CA2433453C - Triazolo[4,5-d]pyrimidine derivatives and their use as purinergic receptor antagonists - Google Patents

Abstract

The use of a compound of formula (I): wherein R1 is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR5R6, NR4COR5, NR4CONR5R6,NR4CO2R7 and NR4SO2R7; R2 is selected from aryl attached via an unsaturated carbon; R3 is selected from H, alkyl, COR5, CO2 R7, CONR5R6, CONR4NR5R6 and SO2R7; R4, R5 and R6 are independently selected from H, alkyl and aryl or where R5 and R6 are in an NR5R6 group, R5 and R6 may be linked to form a heterocyclic group, or where R4,R5 and R6 are in a (CONR4NR5R6) group, R4 and R5 may be linked to form a heterocyclic group; and R7 is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, in the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A2A
receptors, may be beneficial, particularly wherein said disorder is a movement disorder such as Parkinson's disease or said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy, or for neuroprotection in a subject; compounds of formula (I) for use in therapy; and novel compounds of formula (I) per se.

Description

TRIAZOLO[4,5-d]PYRIMIDINE DERIVATIVES AND THEIR USE AS
PURINERGIC RECEPTOR ANTAGONISTS
The present invention relates to triazolo[4,5-d]pyrimidine derivatives and their use in therapy. In particular, the present invention relates to the treatment of disorders in which the reduction of purinergic neurotransmission could be beneficial. The invention relates in particular to the blockade of adenosine receptors and particularly adenosine A2A receptors, and to the treatment of movement disorders such as Parkinson's disease.
Movement disorders constitute a serious health problem, ,especially amongst the elderly sector of the population. These movement disorders are often the result of brain lesions. Disorders involving the basal ganglia which result in movement disorders include Parkinson's disease, Huntington's chorea and Wilson's disease.
Furthermore, dyskinesias often arise as sequelae of cerebral ischaemia and other neurological disorders.
There are four classic symptoms of Parkinson's disease: tremor, rigidity, akinesia and postural changes. The disease is also commonly associated with depression, dementia and overall cognitive decline. Parkinson's disease has a prevalence of 1 per 1,000 of the total population. The incidence increases to 1 per 100 for those aged over years. Degeneration of dopaminergic neurones in the substantia nigra and the subsequent reductions in interstitial concentrations of dopamine in the striatum are critical to the development of Parkinson's disease. Some 80% of cells from the substantia nigra need to be destroyed before the clinical symptoms of Parkinson's disease are manifested.
Current strategies for the treatment of Parkinson's disease are based on transmitter replacement therapy (L-dihydroxyphenylacetic acid (L-DOPA)), inhibition of monoamine oxidase (e.g. Deprenyl~), dopamine receptor agonists (e.g.
bromocriptine and apomorphine) and anticholinergics (e.g. benztrophine, orphenadrine).
Transmitter replacement therapy in particular does not provide consistent clinical benefit, especially after prolonged treatment when "on-off" symptoms develop, and this treatment has also been associated with involuntary movements of athetosis and chorea, nausea and vomiting. Additionally current therapies do not treat the underlying neurodegenerative disorder resulting in a continuing cognitive decline in patients. Despite new drug approvals, there is still a medical need in terms of improved therapies for movement disorders, especially Parkinson's disease. In particular, effective treatments requiring less frequent dosing, effective treatments which are associated with less severe side-effects, and effective treatments which control or reverse the underlying neurodegenerative disorder, are required.
Blockade of AZ adenosine receptors has recently been implicated in the treatment of movement disorders such as Parkinson's disease (Richardson, P.J. et al., Trends Pharmacol. Sci. 1997, 18, 338-344) and in the treatment of cerebral ischaemia (Gao, Y. and Phillis, J.W., Life Sci. 1994, 55, 61-65). The potential utility of adenosine AAA
receptor antagonists in the treatment of movement disorders such as Parkinson's Disease has recently been reviewed (Mally, J. and Stone, T.W., CNS Drugs, 1998, 10, 311-320).
Adenosine is a naturally occurring purine nucleoside which has a wide variety of well-documented regulatory functions and physiological effects. The central nervous system (CNS) effects of this endogenous nucleoside have attracted particular attention in drug discovery, owing to the therapeutic potential of purinergic agents in CNS
disorders (Jacobson, K.A. et al., J. Med. Chem. 1992, 35, 407-422). This therapeutic potential has resulted in considerable recent research endeavour within the field of adenosine receptor agonists and antagonists (Bhagwhat, S.S.; Williams, M. Exp.
Opin. Ther. Patents 1995, 5,547-558).
Adenosine receptors represent a subclass (P1) of the group of purine nucleotide and nucleoside receptors known as purinoreceptors. The main pharmacologically distinct adenosine receptor subtypes are known as Al, AAA, A2B (of high and low affinity) and A3 (Fredholm, B.B., et al., Pharmacol. Rev. 1994, 46, 143-156). The adenosine receptors are present in the CNS (Fredholm, B.B., News Physiol. Sci., 1995, 10, 122-128).
The design of Pl receptor-mediated agents has been reviewed (Jacobson, K.A., Suzuki, F., Drug Dev. Res., 1997, 39, 289-300; Baraldi, P.G. et al., Curr.
Med. Chem.

1995, 2, 707-722), and such compounds are claimed to be useful in the treatment of cerebral ischemia or neurodegenerative disorders, such as Parkinson's disease (Williams, M. and Burnstock, G. Purinergic Approaches Exp. Ther. (1997), 3-26.
Editor: Jacobson, Kenneth A.; Jarvis, Michael F. Publisher: Wiley-Liss, New York, N.Y.) It has been speculated that xanthine derivatives such as caffeine may offer a form of treatment for attention-deficit hyperactivity disorder (ADHD). A number of studies have demonstrated a beneficial effect of caffeine on controlling the symptoms of ADHD (Garfinkel, B.D. et al., Psychiatry, 1981, 26, 395-401). Antagonism of adenosine receptors is thought to account for the majority of the behavioural effects of caffeine in humans and thus blockade of adenosine AaA receptors may account for the observed effects of caffeine in ADHD patients. Therefore a selective AaA
receptor antagonist may provide an effective treatment for ADHD but without the unwanted side-effects associated with current therapy.
Adenosine receptors have been recognised to play an important role in regulation of sleep patterns, and indeed adenosine antagonists such as caffeine exert potent stimulant effects and can be used to prolong wakefulness (Porkka-Heiskanen, T.
et al., Science, 1997, 276, 1265-1268). Recent evidence suggests that a substantial part of the actions of adenosine in regulating sleep is mediated through the adenosine AZA
receptor (Satoh, S., et al., Proc. Natl. Acad. Sci., USA, 1996). Thus, a selective A2a receptor antagonist may be of benefit in counteracting excessive sleepiness in sleep disorders such as hypersomnia or narcolepsy.
It has recently been observed that patients with major depression demonstrate a blunted response to adenosine agonist-induced stimulation in platelets, suggesting that a dysregulation of AaA receptor function may occur during depression (Berk, M.
et al, 2001, Eur. Neuropsyclaopharmacol. 11, 183-186). Experimental evidence in animal models has shown that blockade of AZA receptor function confers antidepressant activity (El Yacoubi, M et al. Br. J. Pharmacol. 2001, 134, 68-77). Thus, A2Areceptor antagonists may offer a novel therapy for the treatment of major depression and other affective disorders in patients.

The pharmacology of adenosine AZA receptors has been reviewed (Ongini, E.;
Fredholm, B.B. Trends Pharmacol. Sci. 1996, 17(10), 364-372). One potential underlying mechanism in the aforementioned treatment of movement disorders by the blockade of A~ adenosine receptors is the evidence of a functional link between adenosine A2A receptors to dopamine Da receptors in the CNS. Some of the early studies (e.g. Ferre, S. et al., Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine DZ receptors in rat striatal membranes.
Proc. Natl.
Acad. Sci. U.S.A. 1991, 88, 7238-41) have been summarised in two more recent articles (Fuxe, K. et al., Adenosine Adenine Nucleotides Mol. Biol. Integr.
Physiol., [Proc. Int. Symp.], 5th (1995), 499-507. Editors: Belardinelli, Luiz; Pelleg, Amir.
Publisher: Kluwer, Boston, Mass.; Ferre, S. et al., Trends Neurosci. 1997, 20, 487).
As a result of these investigations into the functional role of adenosine AaA
receptors in the CNS, especially in vivo studies linking Aa receptors with catalepsy (Ferre et al., Neurosci. Lett. 1991, 130, 162-4; Mandhane, S.N. et al., Eur. J. Pharmacol.
1997, 328, 135-141) investigations have been made into agents which selectively bind to adenosine AaA receptors as potentially effective treatments for Parkinson's disease.
While many of the potential drugs for treatment of Parkinson's disease have shown benefit in the treatment of movement disorders, an advantage of adenosine A2a antagonist therapy is that the underlying neurodegenerative disorder may also be treated. The neuroprotective effect of adenosine A2A antagonists has been reviewed (Ongini, E.; Adami, M.; Ferri, C.; Bertorelli, R., Ann. N. Y. Acad. Sci. 1997, 825(Neuroprotective Agents), 30-48). In particular, compelling recent evidence suggests that blockade of A2A receptor function confers neuroprotection against MPTP-induced neurotoxicity in mice (Chen, J-F., J. Neurosci. 2001, 21, RC143).
In addition, several recent studies have shown that consumption of dietary caffeine, a known adenosine A2A receptor antagonist, is associated with a reduced risk of Parkinson's disease in man (Ascherio, A. et al, Ann Neurol., 2001, 50, 56-63;
Ross G
W, et al., JAMA, 2000, 283, 2674-9). Thus, A2A receptor antagonists may offer a novel treatment for conferring neuroprotection in neurodegenerative diseases such as Parkinson's disease.

~yanthine derivatives have been disclosed as adenosine Aa receptor antagonists as useful for treating various diseases caused by hyperfunctioning of adenosine receptors, such as Parkinson's disease (see, for example, EP-A-565377).

5 One prominent xanthine-derived adenosine AaA selective antagonist is CSC [8-(3-chlorostyryl)caffeine] (Jacobson et al., FEBS Lett., 1993, 323, 141-144).
Theophylline (1,3-dimethylxanthine), a bronchodilator drug which is a mixed antagonist at adenosine A1 and A2A receptors, has been studied clinically. To determine whether a formulation of this adenosine receptor antagonist would be of value in Parkinson's disease an open trial was conducted on 15 Parkinsonian patients, treated for up to 12 weeks with a slow release oral theophylline preparation (150 mg/day), yielding serum theophylline levels of 4.44 mg/L after one week. The patients exhibited significant improvements in mean objective disability scores and 11 reported moderate or marked subjective improvement (Mally, J., Stone, T.W. J.
Pharm. Pharmacol. 1994, 46, 515-517).
KF 17837 [(E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine] is a selective adenosine AZA receptor antagonist which on oral administration significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine AAA receptor agonist, CGS 21680. KF 17837 also reduced the catalepsy induced by haloperidol and reserpine. Moreover, KF 17837 potentiated the anticataleptic effects of a subthreshold dose of L-DOPA plus benserazide, suggesting that KF 17837 is a centrally active adenosine AZA receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine AAA
receptor antagonists (Kanda, T. et al., Eur. J. Pharmacol. 1994, 256, 263-268). The structure activity relationship (SAR) of KF 17837 has been published (Shimada, J. et al., Bioorg. Med. Chem. Lett. 1997, 7, 2349-2352). Recent data has also been provided on the A2A receptor antagonist KW-6002 (Kuwana, Y et al., Soc.
Neurosci.
Abstr. 1997, 23, 119.14; and Kanda, T. et al., Ann. Neurol. 1998, 43(4), 507-513).
New non-xanthine structures sharing these pharmacological properties include SCH
58261 and its derivatives (Baraldi, P.G. et al., Pyrazolo[4,3-a]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives: Potent and Selective AZA Adenosine Antagonists. J.
Med.

Czhem. 1996, 39, 1164-71). SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-a]-1,2,4-triazolo[1,5-c] pyrimidine) is reported as effective in the treatment of movement disorders (Ongini, E. Drug Dev. Res. 1997, 42(2), 63-70) and has been followed up by a later series of compounds (Baraldi, P.G. et al., J.
Med.
Claem. 1998, 41(12), 2126-2133).
The foregoing discussion indicates that a potentially effective treatment for movement disorders in humans would comprise agents which act as antagonists at adenosine AZa.
receptors.
It has now been found that triazolo[4,5-d]pyrimidine derivatives, which are structurally unrelated to known adenosine receptor antagonists, exhibit unexpected antagonist binding affinity at adenosine (P1) receptors, and in particular at the adenosine AaA receptor. Such compounds may therefore be useful for the treatment of disorders in which the blocking of purine receptors, particularly adenosine receptors and more particularly adenosine A2A receptors, may be beneficial. In particular such compounds may be suitable for the treatment of movement disorders, such as disorders of the basal ganglia which result in dyskinesias. Disorders of of particular interest include Parkinson's disease, Alzheimer's disease, spasticity, Huntington's chorea and Wilson's disease.
Such compounds may also be particularly suitable for the treatment of depression, cognitive or memory impairment including Alzheimer's disease, acute or chronic pain, ADHD and narcolepsy, or for neuroprotection.

According to the present invention there is provided the use of a compound of formula (I):

~N
, N N R

(I) wherein Ri is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NRSR6, NR4COR5, NR4CONRSR6, NR4CO2R7 and NR4S02R~;
Ra is selected from aryl attached via an unsaturated carbon;
R3 is selected from H, alkyl, CORS, C02R~, CONRSR&, CONR4NRSR6 and S02R~;
R4, RS and R6 are independently selected from H, alkyl and aryl or where RS
and R6 are in an NRSR6 group, RS and R6 may be linked to form a heterocyclic group, or where R4, RS and R6 are in a (CONR4NRSR6) group, R4 and RS may be linked to form a heterocyclic group; and R~ is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, in the manufacture of a medicament for the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly AZA
receptors, may be beneficial.
As used herein, the term "alkyl" means a branched or unbranched, cyclic or acyclic, saturated or unsaturated (e.g. alkenyl or alkynyl) hydrocarbyl radical which may be substituted or unsubstituted. Where cyclic, the alkyl group is preferably C3 to Cl~, more preferably CS to Clo, more preferably C5, C6 or C~. Where acyclic, the alkyl group is preferably Cl to Clo, more preferably Cl to C6, more preferably methyl, ethyl, propyl (n-propyl or isopropyl), butyl (n-butyl, isobutyl or tertiary-butyl) or pentyl (including n-pentyl and iso-pentyl), more preferably methyl. It will be appreciated therefore that the term "alkyl" as used herein includes alkyl (branched or unbranched), alkenyl (branched or unbranched), alkynyl (branched or unbranched), cycloalkyl, cycloalkenyl and cycloalkynyl.

As used herein, the term "lower alkyl" means methyl, ethyl, propyl (n-propyl or isopropyl) or butyl (n-butyl, isobutyl or tertiary-butyl).
As used herein, the term "aryl" means an aromatic group, such as phenyl or naphthyl, or a heteroaromatic group containing one or more heteroatom(s), such as pyridyl, pyrrolyl, quinolinyl, furanyl, thienyl, oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, imidazolyl, pyrimidinyl, indolyl, pyrazinyl and indazolyl.
As used herein, the term "heteroaryl" means an aromatic group containing one or more heteroatom(s) preferably selected from N, O and S, such as pyridyl, pyrrolyl, quinolinyl, furanyl, thienyl, oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, imidazolyl, pyrimidinyl, indolyl, pyrazinyl and indazolyl.
As used herein, the term "non-aromatic heterocyclyl" means a non-aromatic cyclic group containing one or more heteroatom(s) preferably selected from N, O and S, such as a cyclic amino group (including aziridinyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl) or a cyclic ether (including tetrahydrofuranyl).
As used herein, the term "alkoxy" means alkyl-O-. As used herein, the term "aryloxy"
means aryl-O-.
As used herein, the term "halogen" means a fluorine, chlorine, bromine or iodine radical.
As used herein, the term "prodrug" means any pharmaceutically acceptable prodrug of a compound of the present invention.
Where any of Rl to R14 is selected from alkyl, alkoxy and alkylthio, particularly from alkyl and alkoxy, in accordance with formula (I) as defined above, then that alkyl group, or the alkyl group of the alkoxy or alkylthio group, may be substituted or unsubstituted. Where any of Rl to Rl4is selected from aryl, aryloxy and arylthio, particularly from aryl and aryloxy, in accordance with formula (I) as defined above, then said aryl group, or the aryl group of the aryloxy group, may be substituted or u~substituted. Where RS and R6, or R and R5, are linked to form a heterocyclic group, the heterocyclic group may be substituted or unsubstituted.
Where substituted, there will generally be 1 to 3 substituents present, preferably 1 substituent. Substituents may include:

carbon-containing groups such as alkyl, aryl, (e.g. substituted and unsubstituted phenyl (including alkylphenyl, alkaxyphenyl and halophenyl), arylalkyl; (e.g. substituted and unsubstituted benzyl);

halogen atoms and halogen containing groups such as haloalkyl - (e.g. trifluoromethyl), haloaryl (e.g. chlorophenyl);

oxygen containing groups such as alcohols (e.g. hydroxy, hydroxyalkyl, hydroxyaryl, (aryl)(hydroxy)alkyl), ethers (e.g. alkoxy, aryloxy, alkoxyalkyl, aryloxyalkyl, alkoxyaryl, aryloxyaryl), aldehydes (e.g. carboxaldehyde), ketones (e.g. alkylcarbonyl, arylcarbonyl, alkylcarbonylalkyl, alkylcarbonylaryl, arylcarbonylalkyl, arylcarbonylaryl, arylalkylcarbonyl, arylalkylcarbonylalkyl, arylalkylcarbonylaryl) acids (e.g. carboxy, carboxyalkyl, carboxyaryl), acid derivatives such as esters (e.g. alkoxycarbonyl, aryloxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonylalkyl, alkoxycarbonylaryl, aryloxycarbonylaryl, alkylcarbonyloxy, alkylcarbonyloxyalkyl), amides (e.g. aminocarbonyl, mono- or di-alkylaminocarbonyl, cyclicaminocarbonyl, aminocarbonylalkyl, mono- or di-alkylaminocarbonylalkyl, arylaminocarbonyl or arylalkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino or arylalkylcarbonylamino), carbamates 5 (eg, alkoxycarbonylarnino, aryloxycarbonylamino, arylalkyloxycarbonylamino, aminocarbonyloxy, mono- or di-alkylaminocarbonyloxy, arylaminocarbonyloxy or 10 arylalkylaminocarbonyloxy) and ureas (eg. mono- or di-alkylaminocarbonylamino, arylaminocarbonylamino or arylalkylaminocarbonylamino);
nitrogen containing groups such as amines (e.g. amino, mono- or dialkylamino, cyclicamino, arylamino, aminoalkyl, mono- or dialkylaminoalkyl), azides, nitrites (e.g. cyano, cyanoalkyl), vitro, sulfonamides (e.g. aminosulfonyl, mono- or di-alkylamino sulfonyl, mono- or di-arylaminosulfonyl, alkyl- or aryl-sulfonyl amino, alkyl- or aryl-sulfonyl(alkyl)amino, alkyl- or aryl-sulfonyl(aryl)arnino);
sulfur containing groups such as thiols, thioethers, sulfoxides, and sulfones (e.g. alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, arylthio, arylsulfinyl, arylsulfonyl, arylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl) and heterocyclic groups containing one or more, preferably one, heteroatom, (e.g. thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, oxadiazolyl, thiadiazolyl, aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, tetrahydrofuranyl, pyranyl, . pyronyl, pyridyl, pyrazinyl, pyridazinyl, piperidyl, hexahydroazepinyl, piperazinyl, morpholinyl, thianaphthyl, benzofuranyl, isobenzofuranyl, indolyl, oxyindolyl, isoindolyl, indazolyl, indolinyl, azaindolyl, benzopyranyl,coumarinyl, isocoumarinyl, quinolinyl, isoquinolinyl, naphthridinyl, cinnolinyl, quinazolinyl, pyridopyridyl, benzoxazinyl,quinoxalinyl, chromenyl, chromanyl, isochromanyl, phthalazinyl and carbolinyl).

Where any of Rl to RI4 is selected from aryl or from an aryl-containing group such as aryloxy or arylthio, preferred substituent groups) are selected from halogen, alkyl (substituted or unsubstituted; and where substituted particularly from alkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl), hydroxy, alkoxy, CN, N02, amines (including amino, mono- and di-alkylamino), alkoxycarbonyl, aminocarbonyl, carboxamido, sulfonamido, alkoxycarbonylamino and aryl, and particularly from unsubstituted alkyl, substituted alkyl (including alkoxyalkyl and aminoalkyl), halogen and amines.
In one embodiment, where any of R1 to R14 is directly substituted by an alkyl substituent group, or by an alkyl-containing substituent group (such as alkoxy or alkylcarbonylamino for example), then the alkyl moiety of the substituent group directly attached to any of Ri to R14 may be further substituted by the substituent groups hereinbefore described and particularly by halogen, hydroxy, alkoxy, CN, amines (including amino, mono- and di-alkyl amino) and aryl.
In a further embodiment, where any of Rl to Rl~ is directly substituted by an aryl substitutent group, or by an aryl-containing substituent group (such as aryloxy or a~ylaminocarbonylamino for example), then the aryl moiety of the substituent group directly attached to any of Rl to R14 may be further substituted by the substituent groups hereinbefore described and particularly by halogen, alkyl (substituted or unsubstituted;
and where substituted particularly from alkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl), hydroxy, alkoxy, CN, NO2, amines (including amino, mono- and di-alkylamino), allcoxycarbonyl, aminocarbonyl, carboxamido, sulfonamido, alkoxycarbonylamino and aryl. In a further embodiment, said aryl moiety is substituted by halogen, alkyl (including CF3), hydroxy, alkoxy, CN, amines (including amino, mono- and di-alkyl amino) and NO~. In a further embodiment, said aryl moiety is substituted by unsubstituted alkyl, substituted alkyl (particularly alkoxyalkyl and aminoalkyl), halogen and amines.
The terms "directly substituted" and "directly attached", as used herein, mean that the substituent group is bound directly to any of Rl to R14 without any intervening divalent atoms or groups.
In the compounds of formula (~, Rl is selected from H, alkyl (including branched and unbranched alkyl, substituted and unsubstituted alkyl, and cyclic and acyclic alkyl), aryl (including heteroaryl), alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, (including NH2), NRøCORS, NR4CONRSR6, NR4CO~R~ and NR4SO~R~.
In one embodiment, the compounds of formula (1] are those wherein Rl is selected from alkyl (including branched and unbranched alkyl, substituted and unsubstituted alkyl, and cyclic and acyclic alkyl), aryl (including heteroaryl), alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NRSR6 (including NHa), NR4COR5, NR4CONRSR6, NR4CO~R~ and NR4S02R~.
Preferably, Rl is selected from alkyl (including branched and unbranched alkyl, substituted and unsubstituted alkyl, and cyclic and acyclic alkyl), alkoxy, alkylthio, NRsR6 (including NHZ), NR4COR5, NR4CONRSR6, NR4C02R~ and NR4S02R~, more preferably from NRSRb (including NHZ), NR4COR5, NR4CONRSR6, NR4C02R~ and NR4S02R~, more preferably from NRSR6 (including NH2) and NR4COR5, more preferably from NRSR6 (including NH2) and most preferably from NHS.

VVhere R1 is selected from NRSR6, in one embodiment RS and R6 are independently selected from hydrogen, alkyl and aryl, preferably from hydrogen.
Where Rl is selected from NR4COR5, in one embodiment R4 is hydrogen.
Where Rl is selected from alkyl, Rl is preferably Cl-6 alkyl, more preferably Cl-s saturated alkyl, and more preferably lower alkyl. In one embodiment, RI is selected from substituted alkyl, particularly haloalkyl (including CFA) and arylalkyl (including heteroarylalkyl), and particularly haloalkyl (including CF3).
Preferably, R2 is a heteroaryl group, and preferably a heteroaryl group which is attached to the pyrimidine ring of formula (1] such that at least one heteroatom is adjacent to the unsaturated carbon atom attached to said pyrimidine ring. Preferably, Ra is an N, O or S-containing heteroaryl group. Ra may contain one or more heteroatom(s) selected from N,OandS.
In one embodiment, the aryl group of RZ (including wherein Ra is a heteroaryl group) is not ortho,ortho-disubstituted. Preferably, the aryl group of R~ (including wherein RZ is a heteroaryl group) is not substituted at either ortho position. As used herein, reference to ortho-substitution of the R2 group means the ortho positions of the R2 group relative to the point of attachment of Ra to the pyrimidine moiety of formula (1].
Tn a preferred embodiment, R2 is selected from furyl (including 2-furyl), thienyl (including 2-thienyl), pyridyl (including 2-pyridyl), thiazolyl (including 2-and 5-thiazolyl), pyrazolyl (including 3-pyrazolyl), triazolyl (including 4-triazolyl), pyrrolyl (including 2-pyrrolyl) and oxazolyl (including 5-oxazolyl). In a further embodiment, Ra is selected from 2-furyl, 2-thienyl, 2-thiazolyl, 2-pyridyl, 3-pyrazolyl, 2-pyrrolyl, 4-triazolyl and 5-oxazolyl. In a further preferred embodiment, R2 is selected from furyl, thienyl, pyridyl, thiazolyl and pyrazolyl, and particularly from 2-furyl, 2-thienyl, 2-thiazolyl, 2-pyridyl and 3-pyrazolyl. In a further embodiment, R2 is selected from furyl, thienyl and pyridyl, preferably 2-furyl, 2-thienyl and 2-pyridyl. In a particularly preferred embodiment, R2 is selected from furyl, and preferably from 2-furyl, substituted or unsubstituted.

V~here RZ is other than a heteroaryl group, Ra is preferably phenyl.
In the compounds of formula (1], R3 is selected from H, alkyl (including branched and unbranched alkyl, substituted and unsubstituted alkyl, cyclic and acyclic alkyl), CORS, COZR~, CONRSR6, CONR4NRSR6 and SOaR~.
Where R3 is selected from alkyl, R3 is preferably acyclic alkyl, preferably acyclic Cl_6 alkyl (including alkenyl and alkynyl), preferably acyclic Cl_6 saturated alkyl, preferably lower alkyl. In one embodiment, R3 is selected from substituted or unsubstituted methyl, ethyl and propyl (n-propyl or isopropyl) groups.
Where R3 is selected from alkyl, particularly from saturated acyclic Cl_6 alkyl, particularly from lower alkyl and particularly from methyl, ethyl and propyl, it is preferred that R3 is substituted alkyl. Preferred substituents are aryl (including heteroaryl), cycloalkyl, non-aromatic heterocyclyl, CN, CORS, C02R5, CONRSR6, CONR4NRSR6 and C(=NR4)NR$R6, preferably aryl (including heteroaryl), CONRSR6, C02R5 and CORS (preferably wherein RS is aryl), more preferably aryl (including heteroaryl), CONRSR6 and C02R5, more preferably aryl (including heteroaryl) and CONRSRg, and most preferably aryl (including heteroaryl).
Where R3 is selected from arylalkyl (including heteroarylalkyl), the aryl (including heteroaryl) group may be unsubstituted, or substituted as defined in detail below in respect of the group referred to as Rll. Preferably, the arylalkyl (including heteroarylalkyl group) is an arylmethyl (including heteroarylmethyl) group.
The preferred aryl groups are set out below in detail in respect of the group referred to as Ar.
Where R3 is selected from CONRSR6, R5 and R6 are selected from H, alkyl (including substituted alkyl such as arylalkyl (including heteroarylalkyl)) and aryl (including heteroaryl) or RS and R6 may be linked to form a heterocyclic ring. In one embodiment, RS and R6 are selected from unsubstituted alkyl and arylalkyl (including heteroarylalkyl).
Said aryl groups may be substituted or unsubstituted. In a preferred embodiment one of RS and R6 is hydrogen. In a further preferred embodiment, RS is H and R6 is selected from arylalkyl (including heteroarylalkyl), preferably arylmethyl (including heteroarylmethyl).

In a preferred embodiment, R3 is selected from H and substituted alkyl, preferably wherein said alkyl is substituted by aryl (including heteroaryl) or CONRSR6, and preferably by aryl (including heteroaryl), and more preferably by substituted aryl 5 (including heteroaryl).In one embodiment, R3 is selected from (CR9Rlo)oR8 wherein n is 1 to 6 (preferably n is 1, 2 or 3, and preferably n is 1), R9 and Rlo are independently selected from H, alkyl and aryl, and R$ is selected from aryl (including heteroaryl), cycloalkyl, non-aromatic heterocyclic, CN, CORS, C02R$, CONRSR6, CONRqNR5R6 and C(=NR4)NRSRg, preferably aryl (including heteroaryl), CONRSR6, C02R5 and CORS
10 (preferably wherein RS is aryl), more preferably aryl (including heteroaryl), CONRSR6 and C02R5, more preferably aryl (including heteroaryl) and CONRSR6, and most preferably aryl (including heteroaryl). Preferably, R9 and Rlo are independently selected from H and alkyl (preferably acyclic saturated Cl_6 alkyl, preferably lower alkyl, preferably methyl, ethyl or propyl), more preferably H. Preferably, at least one of R9 and 15 Rlo is hydrogen, and preferably both R9 and Rlo are hydrogen.
Where R8 is aryl (including heteroaryl), the aryl (including heteroaryl) group may be unsubstituted, or may be substituted as defined in detail below for Ril. The preferred aryl groups are set out below in detail in respect of the group referred to as Ar.
Where Rg is selected from CONRSR6, RS and R6 are selected from H, alkyl (including substituted alkyl such as arylalkyl (including heteroarylalkyl)) and aryl (including heteroaryl) or RS and RG may be linked to form a heterocyclic ring. In one embodiment, one or both of RS and R6 are selected from unsubstituted alkyl and arylalkyl (including heteroarylalkyl). In a further embodiment, at least one of RS and R6 is selected from aryl (including heteroaryl). Said aryl group may be substituted or unsubstituted.
In a preferred embodiment, one of R5 and R6 is hydrogen.
Where R8 is selected from CORS, RS is preferably aryl (including heteroaryl).
Where R$ is selected from CO~RS, R5 is preferably alkyl or aryl.
In a further preferred embodiment, R3 is selected from H and (CR9Rlo)nRs, more preferably from (CH~)nRB, preferably wherein R$ is selected from aryl (including Heteroaryl) and CONRsR6, more preferably wherein R8 is selected from aryl (including heteroaryl), and more preferably wherein R$ is selected from substituted aryl (including heteroaryl).
In a further embodiment, R3 is selected from (CR9Rlo)nRn wherein R9, Rlo and n are as defined above and Rl1 is selected from the group consisting of substituted aryl (including heteroaryl) groups, preferably mono-, di- or tri-substituted aryl (including heteroaryl) groups represented by the formula !~r(R12)a(R13)b~14)c wherein .Ar is an aryl (including heteroaryl) group; wherein Rla, R13 and R14 are substituent group(s), the same or different; and wherein a, b and c are 0 or 1 such that a+b+c >_1.
In one embodiment, the group Ar is selected from phenyl. In an alternative embodiment, the group A,r is selected from heteroaryl groups such as those described hereinabove, preferably from mono or bicyclic heteroaryl groups, more preferably from pyridyl (including 2-pyridyl, 3-pyridyl and 4-pyridyl, preferably 2-pyridyl), indolyl (including 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl and 7-indolyl), furyl (including 2-furyl and 3-furyl, preferably 2-furyl), thienyl (including 2-thienyl and 3-thienyl, preferably 2-thienyl), isoindolyl, indolinyl, isoxazolyl, oxazolyl, thiazolyl, pyrazinyl, pyrimidinyl, quinolinyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl, indazolyl, benzodioxolyl and dihydrobenzofuranyl, more preferably from pyridyl (preferably 2-pyridyl), indolyl, furyl (preferably 2-furyl) and thienyl (preferably 2-thienyl), and most preferably from pyridyl (preferably 2-pyridyl), furyl (preferably 2-furyl) and thienyl (preferably 2-thienyl).
In one embodiment, the group Ar is selected from phenyl, pyridyl (preferably 2-pyridyl), furyl (preferably 2-furyl), thienyl (preferably 2-thienyl) and indolyl, and particularly from phenyl, pyridyl (preferably 2-pyridyl), furyl (preferably 2-furyl) and thienyl (preferably 2-thienyl).
The substituent groups R12, Ri3 and RIø may be selected from any of the substituent groups described herein above.
In a preferred embodiment, R12, R13 and R14 are selected from NRsR6 (including NHS, and NHRs) alkyl (substituted or unsubstituted; preferably C1_6 acyclic alkyl), alkoxy (including fluoroalkoxy), halogen (including F, C1, Br and I), N02, CN, hydroxy, NHOH, CHO, CONRSRb, COZRS, NR4COR5 (preferably NHCORS), NRøC02R~
(preferably NHCOZR~), NR4S02R~ (preferably NHSOZR~), OCOaR~ and aryl (including heteroaryl).
In a more preferred embodiment, Rlz, Ris and Rld are selected from NRSR6 (including NHS and NHRS), alkyl (substituted or unsubstituted; and preferably C1_6 acyclic saturated alkyl) and halogen (preferably F or Cl, particularly F).
In a particularly preferred embodiment, R12, R13 and R14 are selected from (including NHZ and NHRS, preferably NHa) and alkyl (substituted or unsubstituted;
preferably Cl_6 acyclic saturated alkyl).
Where Rla, R13 and Ri4 are selected from substituted alkyl, said alkyl is preferably selected from alkoxyalkyl, hydroxyalkyl, aminoalkyl (including NH2-alkyl, mono-alkylaminoalkyl and di-alkylaminoalkyl), haloalkyl (particularly fluoroalkyl (including CF3)), cyanoalkyl, alkylthioalkyl, alkylcarboxyaminoalkyl, alkoxycarbonylaminoalkyl and alkylsulfonylamino, more preferably from alkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl (particularly fluoroalkyl (including CF3)) and most preferably from alkoxyalkyl and aminoalkyl.
In one embodiment, the substituent groups R12, Ri3 and Ri4 are selected from halogen, alkyl (including CF3), hydroxy, alkoxy, alkylthio, CN, amines (including amino, mono-and di-alkyl amino) and NOa.
Where the Ar group is phenyl, the phenyl ring may be mono-, di- or tri-substituted, preferably wherein the substituent group is selected from NRSR6, alkyl, alkoxy, halogen, NO~,, CN, hydroxy, CONR5R4, COaRs, NR4COR5, NR4COaR~, NRa.SO~R~ and OC02R~, as described above, and more preferably from NRSR6 (including NH2 and NHRS, and preferably NH2), alkyl (substituted or unsubstituted; preferably C1_6 acyclic saturated alkyl; and, where substituted, preferably from alkoxyalkyl, hydroxyalkyl, aminoallcyl and haloalkyl (particularly fluoroalkyl (including CF3)), and more preferably from alkoxyalkyl and aminoalkyl) and halogen (preferably F or Cl, particularly F).
Where (a+b+c) is 2 or 3, it is preferred that at least one of the substituent groups is NRSR6, particularly NH2.
Where the Ar group is pyridyl, the pyridyl group (which is preferably a 2-pyridyl group) is preferably mono-substituted, preferably 6-substituted. The preferred substituent groups) are selected from alkyl (including substituted and unsubstituted, saturated and unsaturated (such as alkenyl, including vinyl); and preferably Cl_6 acyclic alkyl), alkoxy, halogen, aryl, N02, NHOH and CHO, as described above, and more preferably from alkyl (substituted or unsubstituted; preferably Cl_6 acyclic saturated alkyl;
and, where substituted, preferably from alkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl (particularly fluoroalkyl (including CF3)), and more preferably from alkoxyalkyl and aminoalkyl).
In a preferred embodiment R3 is selected from CHR9Ri1 wherein R9 and Ril are as defined above, and preferably wherein Ar is substituted pyridyl or substituted phenyl.
Where Ar is substituted phenyl, preferably at least one of Rl2 and R13, or at least one of Riz, Ri3 and R14, is NRsRs, preferably NHS.
In the compounds of formula (~, R4, Rs and R6 are independently selected from H, alkyl (including branched and unbranched alkyl, substituted and unsubstituted alkyl, cyclic and acyclic alkyl) and aryl (including heteroaryl) or where Rs and R6 are in any NRSR6 group, Rs and R6 may be linked to form a heterocyclic ring, or where R4, Rs and R6 are in a (CONR4NRsR6) group, R4 and Rs may be linked to form a heterocyclic ring.
In the compounds of formula (J), R7 is selected from alkyl (including branched and unbranched alkyl, substituted and unsubstituted alkyl, cyclic and acyclic alkyl) and aryl (including heteroaryl).
Where R4 to R7 are independently selected from alkyl, preferably R~ to R~ are selected from Cl-6 alkyl, preferably Cl-6 saturated allcyl and more preferably from lower alkyl.
Where Rs and R6, or R4 and Rs, are linked to form a heterocyclic ring said heterocyclic ring may be saturated, partially unsaturated or aromatic, and is preferably saturated.

aaid heterocyclic ring is preferably a 5, 6 or 7-membered ring, preferably a 5 or 6-membered ring, and may contain one or more further heteroatom(s) preferably selected from N, O and S.
In a preferred embodiment, Rl is NHa, R2 is 2-furyl and R3 is arylmethyl (including heteroarylmethyl).
In one embodiment of the invention, the compounds of formula (I) are selected from those set out in claim 41.
In a further embodiment of the invention, the compounds of formula (I) are selected from those set out in claim 42.
Where chiral the compounds of formula (I) may be in the form of a racemic mixture of pairs of enantiomers or in enantiomerically pure form.
According to a further aspect of the present invention there is provided a method of treating or preventing a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly adenosine A2A
receptors, may be beneficial, the method comprising administration to a subject in need of such treatment an effective dose of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof.
The disorder may be caused by the hyperfunctioning of the purine receptors.
The disorders of particular interest are those in which the blocking of purine receptors, partiucularly adenosine receptors and more particularly adenosine A2a receptors, may be beneficial. These may include movement disorders such as Parkinson's disease, drug-induced Parkinsonism, post-encephalitic Parkinsonism, Parkinsonism induced by poisoning (for example MPTP, manganese, carbon monoxide) and post-traumatic Parkinson's disease (punch-drunk syndrome).
Other movement disorders in which the blocking of purine receptors, may be of benefit include progressive supernuclear palsy, Huntingtons disease, multiple system atrophy, corticobasal degeneration, Wilsons disease, Hallerrorden-Spatz disease, progressive pallidal atrophy, Dopa-responsive dystonia-Parkinsonism, spasticity or other disorders of the basal ganglia which result in abnormal movement or posture.
The present invention may also be effective in treating Parkinson's with on-off 5 phenomena; Parkinson's with freezing (end of dose deterioration); and Parkinson's with prominent dyskinesias.
The compounds of formula (I) may be used or administered in combination with one or more additional drugs useful in the treatment of movement disorders, such as L-10 DOPA or a dopamine agonist, the components being in the same formulation or in separate formulations for administration simultaneously or sequentially.
Other disorders in which the blocking of purine receptors, particularly adenosine receptors and more particularly adenosine AaA receptors may be beneficial include 15 acute and chronic pain; for example neuropathic pain, cancer pain, trigeminal neuralgia, migraine and other conditions associated with cephalic pain, primary and secondary hyperalgesia, inflammatory pain, nociceptive pain, tabes dorsalis, phantom limb pain, spinal cord injury pain, central pain, post-herpetic pain and HIV
pain;
affective disorders including mood disorders such as bipolar disorder, seasonal 20 affective disorder, depression, manic depression, atypical depression and monodepressive disease; central and peripheral nervous system degenerative disorders including corticobasal degeneration, demyelinating disease (multiple sclerosis, disseminated sclerosis), Freidrich's ataxia, motoneurone disease (amyotrophic lateral sclerosis, progressive bulbar atrophy), multiple system atrophy, myelopathy, radiculopathy, peripheral neuropathy (diabetic neuropathy, tabes dorsalis, drug-induced neuropathy, vitamin deficiency), systemic lupus erythamatosis, granulomatous disease, olivo-ponto-cerebellar atrophy, progressive pallidal atrophy, progressive supranuclear palsy, spasticity; schizophrenia and related pyshoses;
cognitive disorders including dementia, Alzheimers Disease, Frontotemporal dementia, multi-infarct dementia, AIDS dementia, dementia associated with Huntingtons Disease, Lewy body dementia, senile dementia, age-related memory impairment, cognitive impairment associated with dementia, Korsakoff syndrome, dementia pugilans; attention disorders such as attention-deficit hyperactivity disorder (ADHD), attention deficit disorder, minimal brain dysfunction, brain-injured child syndrome, hyperkinetic reaction childhood, and hyperactive child syndrome;
central nervous system injury including traumatic brain injury, neurosurgery (surgical trauma), neuroprotection for head injury, raised intracranial pressure, cerebral oedema, hydrocephalus, spinal cord injury; cerebral ischaemia including transient ischaemic attack, stroke (thrombotic stroke, ischaemic stroke, embolic stroke, haemorrhagic stroke, lacunar stroke) subarachnoid haemorrhage, cerebral vasospasm, neuroprotection for stroke, peri-natal asphyxia, drowning, cardiac arrest, subdural haematoma; myocardial ischaemia; muscle ischaemia; sleep disorders such as hypersomnia and narcolepsy; eye disorders such as retinal ischaemia-reperfusion injury and diabetic neuropathy; cardiovascular disorders such as claudication and hypotension; and diabetes and its complications.
According to a further aspect of the present invention there is provided use of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof in the manufacture of a medicament for the treatment or prevention of movement disorders in a subject.
According to a further aspect of the invention there is provided a method of treating or preventing movement disorders comprising administration to a subject in need of such treatment an effective dose of a compound of formula (I) invention or a pharmaceutically acceptable salt or prodrug thereof.
According to a further aspect of the invention there is provided use of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof in the manufacture of a medicament for neuroprotection in a subject.
According to a further aspect of the invention there is provided a method of neuroprotection comprising administration to a subject in need of such treatment an effective dose of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof.
The medicament for or method of neuroprotection may be of use in the treatment of subjects who are suffering from or at risk from a neurodegenerative disorder, such as a movement disorder.

According to a further aspect of the invention, there is provided for use in therapy a compound of formula (I), or a pharmaceutically acceptable salt or prodrug thereof.
The present invention may be employed in respect of a human or animal subject, more preferably a mammal, more preferably a human subject.
According to a further aspect of the present invention, there is provided a compound of formula (I), per se, other than compounds wherein Rl is H and R3 is selected from methyl, more preferably other than compounds wherein Rl is H and R3 is selected from unsubstituted lower alkyl, more preferably other than compounds wherein Rl is H and R3 is selected from unsubstituted alkyl, and more preferably other than compounds wherein Rl is H.
According to a further aspect of the present invention, there is provided a compound of formula (I), per se, other than compounds wherein R3 is methyl, preferably other than compounds wherein R3 is unsubstituted lower alkyl and more preferably other than compounds wherein R3 is unsubstituted allcyl.
According to a further aspect of the invention there is provided a method of preparing the novel compounds of formula (1). Compounds of formula (1) may be prepared according to conventional synthetic methods. For example compounds of formula (1) where Rl is NH2 may be synthesised by standard methods such as those illustrated in Reaction Scheme 1.

Reaction Scheme 1 CI Rz Rz 02N ~ w N 02N ~ w N H2N ( w N
H2N N~NHz H2N N~NHz HZN N~NHz (5) (6) CI ~ Rz Rz N
N N ~ ~~ --1 N N ~ ~ -1 N, I
N NHz H N NHz ~ N NHz (2) (3) (4) Compounds of formula (4) where R3 is alkyl (including arylalkyl, heteroarylalkyl and (CR9RIO)nCO~,Rs) may be prepared from compounds of formula (3) by standard methods such as reaction with an appropriate alkyl halide, or substituted alkyl halide in the presence of a suitable base such as sodium hydride.
Compounds of formula (4) where R3 is (CR9Rlo)nCONRsR6 or (CR9Rlo)nCONR4NR5R6 may be prepared from compounds of formula (4) where R3 is (CR9Rio)nCO~Rs by standard methods such as direct reaction with an appropriate amine or hydrazine or by initial hydrolysis of the ester group CO~,RS to a carboxylic acid followed by reaction with an appropriate amine or hydrazine in the presence of a standard coupling reagent such as DCC.
Compounds of formula (4) where R3 is (CR9R~o)nC(=NR4)NRSR6 may be prepared from compounds of formula (4) where R3 is(CR9Rlo)nCN by standard methods such as treatment with an appropriate amine in the presence of trimethyl aluminium.
Compounds of formula (4) where R3 is(CR9Rlo)nCN may be prepared from compounds of formula (3) by standard methods such as treatment with an appropriate substituted alkyl halide in the presence of a suitable base such as sodium hydride.

Compounds of formula (4) where R3 is CONRSR6 or CONR4NRSR6 may be prepared from compounds of formula (3) by standard methods such as treatment with an appropriate isocyanate (RSNCO or R6NC0) or carbamoyl chloride (RSR6NCOC1 or RSR6NRq.NCOCI).
Compounds of formula (4) where R3 is CORS, C02R~ or SOZR~ may be prepared from compounds of formula (3) by standard methods such as treatment with an appropriate acid chloride (RSCOCI), chloroformate (C1C02R~) or sulphonyl chloride (R~S02C1) in the presence of a suitable base such as triethylamine.
Compounds of formula (3) may be prepared from the known chloro compound of formula (2) by standard methods such as aryl or heteroaryl coupling reactions.
Suitable aryl or heteroaryl coupling reactions would include reaction with an appropriate aryl or heteroarylboronic acid derivative, an aryl or heteroaryl trialkylstannane derivative or an aryl or heteroarylzinc halide derivative in the presence of a suitable catalyst such as a palladium complex.
Compounds of formula (3) may also be prepared from compounds of formula (7) by standard methods such as treatment with isoamyl nitrite. Compounds of formula (7) are either known in the literature or may be prepared from compounds of formula (6) by standard methods such as reduction with hydrogen in the presence of a suitable catalyst such as Pd. Compounds of formula (6) are either known in the literature or may be prepared from the known compound of formula (5) by standard methods such as aryl or heteroaryl coupling reactions as described above.
Compounds of formula (1) where R1 is NRSR6 may be prepared from compounds of formula (4) by standard methods such as reductive amination with an appropriate aldehyde or ketone, or by treatment with an appropriate alkyl halide in the presence of a suitable base.
Compounds of formula (1) where R1 is NR4CONRSR6, wherein R4 is H, may be prepared from compounds of formula (4) by standard methods such as treatment with an appropriate isocyanate (RSNCO or R6NCO) or carbamoyl chloride (RSR6NCOC1).
Compounds of formula (1) where Rl is NR4CONR5R6, wherein R4 is alkyl, may be prepared as described above having first performed an additional alkylation step as described above.
Compounds of formula (1) where RI is NR4CORs, NR4C02R~ or NR4SOZR~, wherein 5 R4 is H, may be prepared from compounds of formula (4) by standard methods such as treatment with an appropriate acid chloride (RSCOCI), chloroformate (C1C02R~) or sulphonyl chloride (R~SOZCI) in the presence of a suitable base. Compounds of formula (1) where Rl is NRq.CORs, NRøC02R~ or NR4S02R~, wherein R4 is alkyl, may be prepared as described above having first performed an additional alkylation 10 step as described above.
Compounds of formula (1) where Rl is NHz may also be synthesised by standard methods such as those illustrated in Reaction Scheme 2.
15 Reaction Scheme 2 CI I
H2N ~ N H2N ~ N
CI N NHz H i N NHz (8) (8) CI Rz N N I ~ -1 N,N
N NHz r N NHz (10) (4) Compounds of formula (4) where R3 is alkyl (including arylalkyl, heteroarylalkyl and (CR9Rlo)nCOzRs) may be prepared from compounds of formula (10) by standard methods such as aryl or heteroaryl coupling reactions as described above.
Compounds 20 of formula (10) where R3 is alkyl are either known in the literature or may be prepared by methods analogous to those described in the literature. For example compounds of formula (10) where R3 is alkyl may be prepared from compounds of formula (9) where R3 is alkyl by standard methods such as treatment with isoamyl nitrite.
Compounds of formula (9) where R3 is alkyl are either known in the literature or may lie prepared by methods analogous to those described in the literature such as the treatment of the known compound of formula (g) with an appropriate amine in a suitable solvent preferably at elevated temperature.
Compounds of formula (1) where Rl is NH2 may also be synthesised by standard methods such as those illustrated in Reaction Scheme 3.
Reaction Scheme 3 02N ~ N 02N ~ N 02N ~ N
I ~ = I ~ --~ I

(11 ) (12) (13) Rx 2 N wN 02N ~N
rv, I ~, t ~ I J~

Rs Rs (4) (15) (14) Compounds of formula (4) where R3 is alkyl (including arylalkyl, heteroarylalkyl and (CR9Rlo)nC02Rs) may be prepared from compounds of formula (15) where R3 is alkyl by standard methods such as treatment with isoamyl nitrite. Compounds of formula (15) where R3 is alkyl may be prepared from compounds of formula (14) where R3 is alkyl by standard methods such as reduction with hydrogen in the presence of a suitable catalyst such as Pd. Compounds of formula (14) where R3 is alkyl are either known in the literature or may be prepared from compounds of formula (13), where X
is a suitable leaving group such as a tosylate or triflate group, by standard methods such as treatment with a suitable amine in the presence of a suitable base such as triethylamine. Compounds of formula (13) where X is a suitable leaving group are either known in the literature or may be prepared from compounds of formula (12) by standard methods such as treatment with tosyl chloride or triflic anhydride in the prence of a suitable base such as triethylamine or 2,6-dimethylpyridine.
Compounds of formula (12) are either known in the literature or may be prepared from the known compound of formula (11) by standard methods such as aryl or heteroaryl coupling reactions as described above.
Other compounds of formula (1) may be prepared by standard methods such as those illustrated in Reaction Scheme 4.
Reaction Scheme 4 NN I ~N NN I ~N
, / N~~ / N~~

(16) (1 ) Compounds of formula (1) where Rl is H, alkyl or aryl may be prepared from compounds of formula (16) where Rl is H, alkyl or aryl by standard methods such as aryl or heteroaryl coupling reactions as described above. Compounds of formula (16) where Rl is H, alkyl or aryl are either known in the literature or may be prepared by methods analogous to those described in the literature:
Compounds of formula (1) where R1 is alkoxy, aryloxy, alkylthio, arylthio, CN
or NRSR6 may be prepared from compounds of formula (1) where Rl is halogen by standard methods such as nucleophilic displacement using an appropriate nucleophilic reagent such as an alcohol, thiol, cyanide or amine (HNRSR6) in the presence of a suitable base if required. Compounds of formula (1) where Rl is halogen may be prepared from compounds of formula (16) where Rl is halogen as described above.
Compounds of formula (16) where Rl is halogen are either known in the literature or may be prepared by methods analogous to those described in the literature.
Compounds of formula (1) where Rl is NR4CONR5R6, NR4COR5, NR4COZR~ or NR4SOZR~, wherein R4 is alkyl or aryl, may be prepared from compounds of formula (1) where Rl is NR$R6, wherein RS is H and R6 is alkyl or aryl, by the methods described above.

Iri certain cases it may be advantageous to prepare a compound of formula (1) where R3 is selected to perform the function of a protecting group, for example a suitable protecting group would be a benzyl group or substituted benzyl group such as a 3,4-dimethoxybenzyl group. Compounds of this nature may prepared as described above and the protecting group R3 may be removed by standard methods such as treatment with, for example, TFA to give a compound of formula (1) where R3 is H.
Compounds of formula (1) where R3 is H may then be used to prepare other compounds of formula (1), where R3 is as previously defined, by the methods described above.
In the compounds of formula (1) the groups R1, R~ and R3 may be further substituted as defined above and it will be appreciated-by those skilled in the art that suitable substituent groups may be introduced directly according to the methods described above or alternatively may be introduced by further functionalisation of substituent groups which themselves are introduced directly. For example where the group Rl, Ra or R3 contains a nitro substituent this may be reduced by standard methods to an amino group. The resulting amino group may then be further transformed by a variety of standard methods known to those skilled in the art to an alternative functional group such as an amide, urea, carbamate, sulphonamide or alkylamine.
According to a further aspect of the invention, there is provided a pharmaceutical composition comprising a compound of formula (I) in combination with a pharmaceutically acceptable carrier or excipient and a method of making such a composition comprising combining a compound of formula (I) with a pharmaceutically acceptable carrier or excipient.
The pharmaceutical compositions employed in the present invention comprise a compound of the present invention, or pharmaceutically acceptable salts or prodrugs thereof, and may also contain a pharmaceutically acceptable earner and optionally other therapeutic ingredients known to those skilled in the art. The term, "pharmaceutically acceptable salts", refers to salts prepared from pharmaceutically acceptable non-toxic acids including inorganic acids and organic acids.

V~here the compounds of formula (I) are basic, salts may be prepared from pharmaceutically acceptable non-toxic acids including inorganic and organic acids.
Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethenesulfonic, fumaric, gluconic, glutamic, hippuric, hydrobromic, hydrochloric, isethionic, lactic, malefic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, oxalic, p-toluenesulfonic and the like. Particularly preferred are hydrochloric, hydrobromic, phosphoric, and sulfuric acids, and most particularly preferred is the hydrochloride salt.
Any suitable route of administration may be employed for providing the patient with an effective dosage of a compound of the present invention. For example, oral, rectal, parenteral (intravenous, intramuscular); fransderinal, subcutaneous, and the like may be employed. Dosage forms include tablets, troches, dispersions, suspensions, solutions, capsules, patches, and the like. The most suitable route in any given case will depend on the severity of the condition being treated. The most preferred route of administration of the present invention is the oral route. The compositions may be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.
In practical use, the compounds can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g. oral or parenteral (e.g.
intravenous). Tn preparing the compositions for oral dosage form, any of the usual pharmaceutical media may be employed as carriers, such as, for example, water, glycols, oils, alcohols, flavouring agents, preservatives, colouring agents, and the like in the case of oral liquid preparations (such as suspensions, solutions and elixirs) or aerosols; or carriers such as starches, sugars, micro-crystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be used in the case of oral solid preparations such as, for example, powders, capsules, and tablets, with the solid oral preparations being preferred over the liquid preparations.
The most preferred solid oral preparation is tablets.

Because of their ease of administration, tablets and capsules represent the most advantageous oral dosage unit form in which case solid pharmaceutical carriers are employed. If desired, tablets may be coated by standard aqueous or non-aqueous techniques.

In addition to the common dosage forms set out above, the compounds may also be administered by controlled release means and/or delivery devices such as those described in United States Patent Nos.: 3,845,770; 3,916,899; 3,536,809;
3,598,123; 3,630,200; 4,008,719; 4,687,660; and 4,769,027, the disclosures of 10 which are hereby incorporated by reference.
Pharmaceutical compositions employed in the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets, or tablets, or aerosol sprays each containing a predetermined amount of the active ingredient as a 15 powder or granules, a solution or a suspension in an aqueous liquid, an oil-in-water emulsion, or a water-in-oil liquid emulsion. Such compositions may be prepared by any of the methods of pharmacy, but all methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and 20 intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation.
For example, a tablet may be prepared by compression or moulding, optionally with 25 one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, a lubricant, an inert diluent, and/or a surface active or dispersing agent. Moulded tablets may be made by moulding in a suitable machine a mixture of the powdered compound moistened with 30 an inert liquid diluent.
The invention is further defined by reference to the following examples. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practised without departing from the purpose and interest of this invention.
EXAMPLES
Synthetic Examples The invention is illustrated with reference to the following Examples, as set out in Table 1.
Table 1 Example Structure Compound Name 7-(2-furyl)-1H [1,2,3]triazolo[4,5-1 N ~N
d]pyrimidine-5-amine .N
J..

N
NHz H

o N,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-2 NN ~ N'r~N (2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-' ~
i 5-amine i T~

F

-\
O

3-(2-fluorobenzyl)-7-(2-furyl)-3H

3 N;N
N~NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine i F

O

N 7-(2-furyl)-3-(3-nitrobenzyl)-3H-N

N
i ~N
~

N [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NHi OzN

-\
\ 0 N N 3-(3-aminobenzyl)-7-(2-furyl)-3H

5 , NN I N~NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine HxN

o methyl 3-(5-amino-7-(2-furyl)-3H-NN I N~NH [1,2,3]triazolo[4,5-d]pyrimidin-3-i s yl)methylbenzoate MeOz N N 3-(3,S-dimethoxybenzyl)-7-(2-furyl)-3H
I, Me0- 'N N~NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine Me~O
-\
1 c 3-(5-chloro-2-thienyl)methyl-7-(2-furyl)-3H-H N ~N
ci s N~N I N~NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N-(3-(5-amino-7-(2-furyl)-3H
_, Me N\=( H NN i'N [1,2,3]triazolo[4,5-d]pyrimidin-3-ots~~N/ \ N N'lNH2 yl)methyl)phenyl-(1-methyl-1H-imidazol-4-yl)sulphonamide -0 5-amino-N-benzyl-7-(2-furyl)-3H
~~ I N~NHz [1,2,3]triazolo[4,5-d]pyrimidin-3-ylcarboxamide _, O
11 N" I ~ ~-(2-furyl)-3-(3-methoxybenzyl)-3H
N NHi [1,2,3]triazolo[4,5-d]pyrimidine-5-amine Me0 7-(2-furyl)-3-(2-nitrobenzyl)-3H
n N~N I N
1G ~ N~NHs [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NOx O
3-(2-aminobenzyl)-7-(2-furyl)-3H
NN I N
13 ~ N~NHz [1,2,3]triazolo[4,5-d]pyrimidine-S-amine i NH=
-\
ethyl 5-amino-7-(2-furyl)-3H
14 N;N I ~ [1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate N NHZ
COZEt O
3-(3-cyanobenzyl)-7-(2-furyl)-3H-N NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NC

t _.

NN i N 7-(2-furyl)-3-(3-(3-pyridyl)propyl)-3H-16 N~''~N~ (1,2,3]triazolo(4,5-d]pyrimidine-5-amine N
-\
\a 17 K" i ,~ 7-(2-furyl)-3-(3-trifluoromethylbenzyl)-3H
i ' [1,2,3]triazolo(4,5-d]pyrimidine-5-amine F
F
-\
\ O
,N I ~~ 7-(2-furyl)-3-(3-hydroxybenzyl)-3H
1g / \ ~ N NHS (1,2,3]triazolo[4,5-d]pyrimidine-5-amine HO
~s ~. ~ 7-(5-methyl-2-furyl)-1H [1,2,3]triazolo[4,5-~N ~ ~N d]pyrimidine-5-amine N
N N-h -\
3-(2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-20 '" i '~
[ 1,2,3]triazolo[4,5-d]pyrimidine-5-amine F
~N
~ N 7-(1H-pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-21 N N ~ /~ d]pyrimidine-5-amine N N-IZ
\ s 3-(2-fluorobenzyl)-7-(5-thiazolyl)-3H-22 ~ I ,N
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine I F
-\
\ O
N ~~ 7-(2-furyl)-3-(3-methylbenzyl)-3H
23 / \ ~ I N NHx [1,2,3]triazolo[4,5-d]pyrimidine-5-amine _\
\o 7-(2-furyl)-3-(2-pyridylmethyl)-3H
NN ~ ~N
N- 'NFLt [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N

7-(2-furyl)-3-(3-pyridylmethyl)-3H-2S N w [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N
-\
(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-26 ~N ~ N~~ d]pyrimidin-3-yl)acetic acid ~b 3-(3-chlorobenzyl)-7-(2-furyl)-3H-27 ~N ~ ~~
/ \ N NHi [1,2,3]triazolo[4,5-d]pyrimidine-5-amine -3=(2-fluorobenzyl)-7-(1H pyrazol-3-yl)-3H

28 ~ ~ ~N
"'~"~ [1,2,3]triazolo[4,5-d]pyrimidine-S-amine -\
7-(2-furyl)-3-methyl-3H [1,2,3]triazolo[4,5-j~ ~ N~NHx d]PYri~~ne-5-amine HOC
-\

(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5 ~N
HzN~ N~NHz d]pyrimidin-3-yl)acetamide ~?~r~0 (5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-31 N N ~ ~~ d]pyrimidin-3-yl)-N-(3-/ v N
chlorophenyl)acetamide ~b 7-(2-furyl)-3-(6-methoxy-2-pyridylmethyl)-N NHS 3H-[1,2,3]triazolo[4,5-d]pyrimidine-S-amine H,C
-\
\ O
7-(2-furyl)-3-(2-thienylmethyl)-3H
33 ~N ~ ~N
~N~-~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine 1v 3-(2-fluorobenzyl)-7-(2-thiazolyl)-3H
34 ' [1,2,3]triazolo[4,5-d]pyrimidine-5-amine I F
3-(2-fluorobenzyl)-7-(2-thienyl)-3H
35 "
H "~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine i F
CHI
3-(3-aminobenzyl)-7-(5-methyl-2-furyl)-3H-36 'H i '~"
N~HH~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine i~
Ha ~b 37 ~H i ,~ 7-(2=furyl)=3=(6-methyl-2-pyridylmethyl)-3H-N NH, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine H, ~CH~
3-(2-fluorobenzyl)-7-(5-methyl-2-thiazolyl)-N NHS 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine F
tart-butyl N-(3-(5-amino-7-(2-furyl)-3H-39 ~~~ / "~ I ~~ [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate \°
H'~'° N N i ,~ 3-(2,5-dimethoxybenzyl)-7-(2-furyl)-3H
H N NHi [1,2,3]triazolo[4,5-d]pyrimidine-5-amine H C~' O
3-(2,6-difluorobenzyl)-7-(2-furyl)-3H-41 '' I ~H
[ 1,2,3]triazolo[4,5-d]pyrimidine-5-amine ' F
H~
3-(2-fluorobenzyl)-7-(4-methyl-2-thiazolyl)-N H
~ ~NH~ 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine F

-'\
7-(2-thienyl)-1H-[1,2,3]triazolo[4,5-43 ,,N \N
d]pyrimidine-5-amine N
6-chloro-N-(7-(2-furyl)-1H-44 ~N ~ \~N ° [1,2,3]triazolo[4,5-d]pyrimidin-5-yl)pyridine-N Nj 'N ~ \
3-carboxamide i ,N 3-(3-nitrobenzyl)-7-(5-thiazolyl)-3H-45 ~NHi r ~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~b -- 3=(3=amin~methylbenzyl)'-7=(2-furyl)-3H-46 '~N ~ .~
r \ N '~'' [1,2,3]triazolo[4,5-d]pyrimidine-5-amine HiN
\ ° 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-47 \ '~H I N' -NH, d]pyrimidin-3-ylmethyl)-N,N-r H,~, ~ dimethylbenzamide H,C
-\
\ s ~N ~ ,N .3-(3-aminobenzyl)-7-(2-thienyl)-3H
4g r \ N_ 'NHi [1,2,3]triazolo[4,5-d]pyrimidine-5-amine -\
O
3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5 a I wN
49 r ~ '~'"~ d]pyrimidin-3-ylmethyl)-N-methylbenzamide _\
\s "N ~ ,N 3-(3-aminobenzyl)-7-(5-thiazolyl)-3H
50 r \ N"NHi [1~2a3]triazolo[4,5-d]pyrimidine-5-amine H,N
-\
\ O
3-(2-fluoro-5-methoxybenzyl)-7-(2-furyl)-3H
°~ N NFLi _ 51 F"' "(N ~ ~ [1,2,3]triazolo 4,5 d midine-5-amine F

52 (5-ono-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-ON ~ N
~ N~~NH~ d]pyrimidin-3-yl)-N-(2-pyridyl)acetamide / = N
/?/~O
~ b (5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-53 N" ~ ~" d]pyrimidin-3-yl)-N-(2-r ~ N'~~s N~ pyridylmethyl)acetamide (5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-54 ~," ~N
/ ~ "~ ~ N~~,~ d]pyrimidin-3-yl)-N-phenylacetamide ~b 3-(3;5-di-nitrobenzyl)-7-(2=furyl)-3H
55 °_ ~ ~ ~N ~ ~N~ [ rixnidine-5-amine [1,2,3]triazolo 4,5-d]py o .MO
CHe ~b 7-(5-methyl-2-furyl)-3-(3-nitrobenzyl)-3H
56 ' N NN~ [1,2,3]triazolo[4,5-d]pyrirnidine-5-amine O -N~
O
~b 57 ,N ~ ~~ 3-(2,3-difluorobenzyl)-7-(2-furyl)-3H-" ""a [1,2,3]triazolo[4,5-d]pyrimidine-5-amine F
_\
O
3-(2,4-difluorobenzyl)-7-(2-furyl)-3H
SS ~" ~ ~
"\N N"N1s [1,2,3]triazolo[4,5-d]pyrimidine-5-amine F
F
CHI
7-(5-methyl-2-furyl)-3-(6-methyl-2-5g NH I H"NH, pyridylmethyl)-3H-[1,2,3]triazolo[4,5-r~
d]pyrimidine-5-amine HoC
CHI
3-(2,6-difluorobenzyl)-7-(5-methyl-2-furyl)-iN ~ ~N
N"NHi 3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine r~
F

a~

' 7-(5-methyl-2-furyl)-3-(2-thienylmethyl)-3H

~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~_ s 3-(3-chlorobenzyl)-7-(5-methyl-2-furyl)-3H

62 '" i ,x " "~ 1,2,3]triazolo[4,5-d]pyrimidine-5-amine i~
a -\

7-(2-furyl)-3-(4-methoxy-2-pyridylmethyl)-c~' "~,, ~ ~;~~.,3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine =
/~

_\

N 7-(2-furyl)-3-(2-methylbenzyl)-3H

64 ~N
O [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~ ~~_ " 3-(2,5-difluorobenzyl)-7-(2-furyl)-3H

65 ~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine F '~ ~ ~"~, /:

F

~b N N 7-(2-furyl)-3-(2-methoxy-5-nitrobenzyl)-3H
,"

66 i [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~_"'~ ~ "'~"'_ CH=
3-(5-amino-7-(5-methyl-2-furyl)-3H

67 "~H ~ N"HN, [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-o N-methylbenzamide N
H~

N-(3-(5-amino-7-(2-furyl)-3H

68 ~ ~ '~" ~ ~~ [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide 'o " 3-(2-fluorobenzyl)-7-(5-oxazolyl)-3H-69 ~ ~~"
~

N"NH= [~,2,3]triazolo[4,5-d]pyrimidine-5-amine F

3-(4-chloro-2-pyridylmethyl)-7-(2-furyl)-3H-7O ~N \N
'' ~ N~.~,.~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /~
N

-\
O

3-(6-fluoro-2-pyridylmethyl)-7-(2-furyl)-3H-N

'~

/ \ N NN, [1,2,3]triazolo(4,5-d]pyrimidine-5-amine ~N

CHI

3-(2-methoxybenzyl)-7-(5-methyl-2-furyl)-N

i ~ ~N
N~

NH~ 3H [1,2,3]triazolo(4,5-d]pyrimidine-5-amine (0 H~

CFio b tent-butyl N-(3-(5-amino-7-(5-methyl-2-furyl)-73 ~i'N i ;~ 3H [1,2,3]triazolo(4,5-d]pyrimidine-3-' N NHs ~' ylmethyl)benzyl)carbamate ~H~
3-(2-aminobenzyl)-7-(5-methyl-2-furyl)-3H

74 N" I ,~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N NHS
hydrochloride NHi ~b \N 3-(3,5-diaminobenzyl)-7-(2-furyl)-3H

75 I [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~ ~ \ N'~~' CHI
3-(3-aminomethylbenzyl)-7-(5-methyl-2-76 ~N I N" furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-NHi ~

i amine hydrochloride NHi -\

O
7-(2-furyl)-3-(2-methoxybenzyl)-3H-I ~N

N"NH= [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /

OMe ' \
O
-(2-fluoro-5-nitrobenzyl)-7-(2-furyl)-3H
N w i 7g N [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~'' / ~ ~ I N~

F

\o ~N ~~
3-(5-amino-2-fluorobenzyl)-7-(2-furyl)-3H
~ ~

NxN / \ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N NHS

F

3-(2-fluorobenzyl)-7-(1H-triazol-4-yl)-3H-N

8O '~
~ ~. [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N NHi F

s 3-(6-chloro-2-pyridylmethyl)-7-(5-methyl-2-81 ~N ~ ~N furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-~

~_ amine N
I

\ b 7-(5-methyl-2-furyl)-3-(6-phenyl-2-82 "N ~ ~.~", pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine si r-n N 3-(3-aminobenzyl)-7-(2-thiazolyl)-3H-~

3 ~
~
~

N NNi [1,2,3]tnazolo[4,5-d]pynmidine-5-amore HiN

- 3-(5-amino-2-fluorobenzyl)-7-(5-methyl-2-\ V

84 N ~N furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-I
H~

i ~ N ~' amine hydrochloride F

N-(3-(5-amino-7-(2-furyl)-3H

85 '~N ~ NJ\ [1,2,3]triazolo[4,5-d]pyrimidin-3-,~ ylmethyl)benzyl)-3-methylbutanamide 7-(5-methyl-2-furyl)-3-(4-nitro-2-86 p ~N ~ ~N pyridylmethyl)-3H-[1,2,3]triazolo[4,5-~N
o / \ N NHs d]pyrimidine-5-amine N

- ~ 3-(4-hydroxylamino-2-pyridylmethyl)-7-(5-\ o 87 ~N ~ \N methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-.
,N

N Nlii d]pyrimidine-5-amine N

-\
\ o ,,N '~ 7-(2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H

N NH, L1,2,3]triazolo[4,5-d]pyrimidine-5-amine O -NV
O
-\

\ O
N 3-(3-amino-2-methylbenzyl)-7-(2-furyl)-3H-N "Ha L1,2,3]triazolo[4,5-d]pyrimidine-5-amine -Ha CH, \ o 90 , ~ ~ 3-(3-amino-4-methylbenzyl)-7-(2-furyl)-3H

"~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3,5-dimethylisoxazol-4-ylmethyl)-7-(2-91 H~ "~N ~ ~ furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-NH, N~

o amine CHI

-\
\ o 92 ~" i ~~ 7-(2-furyl)-3-(3-methyl-2-nitrobenzyl)-3H

" "H

= [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N o H,C
O

-\
3-cyclohexylmethyl-7-(2-furyl)-3H

93 NN I \N
N" [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NHz _v \

7-(2-furyl)-3-(3-methyl-4-nitrobenzyl)-3H-"

o [1,2,3]triazolo[4,5-d]pyrimidine-5-amine / ~
"'~

.

7-(2-furyl)-3-(3-methyl-2-pyridylmethyl)-3H-95 NN \N
N- ' [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NH
N

-\
\ o ' ~-(2-furyl)-3-(5-methyl-2-nitrobenzyl)-3H
N

96 ~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~
~
" N"' N ' o' \ O

N 3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-97 ~
I ~

/ ' ''"' [1,2,3]triazolo[4,5-d]pyrimidine-5-amine z.

~b N 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-\N

98 ~
N
N"NH

r \ d]pyrimidin-3-ylmethyl)benzoic , acid HO
O

N N 3-(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-N

99 ~
\ N"NH= d]pyrimidin-3-ylmethyl)benzamide / ' H=N
O

-\
\ O

" 7-(2-furyl)-3-(2-methylthiazol-4-ylmethyl)-100 ~ ~"
-~

""= 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine H,O

3-(3-aminomethylbenzyl)-7-(1H
pyrazol-3-101 =N ~ N~"~ yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-/\
amine \ b 3-(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-102 N N ~ ~~NH, d]pyrimidin-3-ylmethyl)-N-isopropyl-N-' r CH methylbenzamide H,~ ' r Ho~ O

\ 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-103 "~" ~ ~"~ d]pyrimidin-3-ylmethyl)-N-isopropylbenzamide a 3-(2-amino-5-methylbenzyl)-7-(2-furyl)-3H

NN ~ ~N
H,C ~ N"NH= [1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-cyano-2-pyridylmethyl)-7-(2-furyl)-3H-lOS ~" ~ ~"
~" ~NH, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine -\
\ o 7-(2-furyl)-3-(5-methyl-2-pyrazinylmethyl)-106 ~N I 'N
NON", 3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine W
Hs \ o 107 "N I '~ 7-(2-furyl)-3-(~-quinolinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine /"
_v 10~ ~ I '~ 7-(2-furyl)-3-(2-phenylthiazol-4-ylmethyl)-N N~ 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine \ S 7-(4-methyl-2-thiazolyl)-3-(3-nitrobenzyl)-'N I \~
""° 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine o ~M

-\
\ o 3-(4-chloro-3-nitrobenzyl)-7-(2-furyl)-3H-'~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine O ~N' O
-\
\ O
3-(1,2,5-benzoxadiazol-5-yl)-7-(2-furyl)-3H
111 'N I , N~'= [1,2,3]triazolo[4,5-d]pyrimidine-5-amine Ni l I /
~N
-\
° 7-(2-furyl)-3-(6-methoxymethyl-2-112 'N ~ N"NH, pyridylmethyl)-3H-[1,2,3]triazolo[4,5-sr ° d)pyrimidine-5-amine _\
3-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-113 N N I '~N
N"NHi d]pyrimidine-5-amine v/
3-(3-amino-4-chlorobenzyl)-7-(2-furyl)-3H

[1,2,3]triazolo[4,5-d]pyrimidine-5-amine iN 'N

-\

7-(2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-115 ay ~N ~ ~ ~N
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine o~N N"NHi _ \ b 7-(2-furyl)-3-(4-hydroxylamino-2-116 "~, ~ pyndylmethyl)-3H [1,2,3]triazolo[4,5-"

Ho NH d]pyrimidine-5-amine N
\~

7-(2-furyl)-3-(6-methyl-4-nitro-2-117 N ~iN ~ pyridylmethyl)-3H-[1,2,3]triazolo[4,5-O

=
N
N

\ N d]pyrimidine-5-amine _\
7-(2-furyl)-3-(4-hydroxylamino-6-methyl-2-11~ N "N ~ ~~ pyridylmethyl)-3H-[1,2,3]triazolo[4,5-H_ _ N NHz d]pyrimidine-5-amine HOC

-\
\ O
~ -(4-chloro-2-nitrobenzyl)-7-(2-furyl)-3H-N ~

~

_ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NH~

G \ / ..
N--\
\ o N -(2-amino-4-chlorobenzyl)-7-(2-furyl)-3H-12O ~ ~N

~

N"~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine G \ /

NHi ~b 3-(4-cyanobenzyl)-7-(2-furyl)-3H-121 ,N ~N
'~ ~ N~~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine _ \ \ 3-(3,4-dimethoxybenzyl)-7-(2-furyl)-3H

122 ~N ~ N" [1,2~3]triazolo[4,5-d]pyrimidine-5-amine NHi H,~
~

trifluoroacetate salt /

~CH~

CHI

7-(5-methyl-2-furyl)-3-(3-methyl-4-123 ~N ~ ~~~N nitrobenzyl)-3H-[1,2,3]triazolo[4,5-N"NHi ~,. ~ / d]pyrimidine-5-amine H,C

3-(4-amino-3-methylbenzyl)-7-(5-methyl-2-124 ~N ~ ~~~N furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-N"NHi H \ i amine H~

O

7-(2-furyl)-3-(5-methyl-3-oxazolyl)-3H

125 ~N ~ 'N
J' 3]triazolo[4 rimidine-5-amine 5-d]
[1 N~ , N , py , H,C /
_i _v 7-(2-furyl)-3-(3-methyl-4-pyridylmethyl)-3H-126 ~N ~ '~N
_H3 N N"NH, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine \/

_~
' 3-(1,2,5-benzothiadiazol-4-ylmethyl)-7-(2-127 NN ~ N" furyl)-3H [1,2,3]triazolo[4,5-d]pyrimidine-5-NHz amine NI ~N
S

-\
' O

7-(2-furyl)-3-(2-pyrazinylmethyl)-3H-N

p ~ ~ N

N"NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine \o N 3-(4-fluoro-3-nitrobenzyl)-7-(2-furyl)-3H

129 ~ ~
~
N NH

z [1,2,3].triazolo[4,5-d]pyrimidine-5-amine O -M
~O

3-(3-nitrobenzyl)-7-phenyl-3H

/ \ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NN, O .N~
~O

7-(2-furyl)-3-(4-methyl-2-pyridylmethyl)-3H

131 ~N 'N
N' ~ ~N,~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine H,C CH, _ H,~ tent-butyl N-(2-(5-amino-7-(2-furyl)-3H
~ o 132 [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-~' N N ~ '~

N N~ 4_pyridylmethyl)carbamate ~' N

~ o " I . 7-(2-furyl)-3-(3-methoxy-4-nitrobenzyl)-3H-133 "l~"
N NN, [1'2,3]triazolo[4,5-d]pyrimidine-5-amine N
H~o_o ~ o 7-(2-furyl)-3-(4-nitrobenzyl)-3H-134 ";" I \~~"
N"NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine °;r. / v N N I , 3-(6-ethyl-2-pyridylmethyl)-7-(2-furyl)-3H
135 / \ ~ N"NHi [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~N
H,c \~
3-(2-ethyl-4-pyridylmethyl)-7-(2-furyl)-3H
136 ~N ~ ~NH, v [1,2,3]triazolo[4,5-d]pyrimidine-5-amine H,C
\ O
tent-butyl 7-(5-amino-7-(2-furyl)-3H-,N I ~
137 N'N N NHx [1,2,3]triazolo[4,5-d]pyrimidine-3-~Ha ylmethyl)indole-1-carboxylate O--~-CHs CH, \~
tart-butyl 4-(5-amino-7-(2-furyl)-3H-qN ~ ~ N
13~ ~ ~ N"NHi [1,2,3]triazolo[4,5-d]pyrimidine-3-H~C O N ~ ylmethyl)indole-1-carboxylate H~C~' 139 ~>" ~ ~~N 7-(2-furyl)-3-(4-indolylmethyl)-3H-N"NHi [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N I
° tart-butyl N-(4-(5-amino-7-(2-furyl)-3H-140 ° "'°~~'~ N'' ~ ~ [1,2,3]triazolo[4,5-d]pyrimidine-3-~" ri "H= ylmethyl)benzyl)carbamate -\
\ o 3-(4-aminobenzyl)-7-(2-furyl)-3H-141 ~N I ~N
J.NHs [1,2,3]triazolo[4,5-d]pyrimidine-5-amine HzN
-\
\ ° tent-butyl 5-(5-amino-7-(2-furyl)-3H
142 H,°~~ ~;N I ,~N [1,2,3]triazolo[4,5-d]pyrimidine-3-H3° N"NH, °~N / ~ ylmethyl)indole-1-carboxylate \ b tent-butyl N-(4-(5-amino-7-(2-furyl)-3H-143 H a~ ' N" I ~ [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-F N
°~ ' \ N NH2 2-fluorophenyl)carbamate N
-\
O
3-(4-aminomethylbenzyl)-7-(2-furyl)-3H
144 .,N ~N
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine !v -\
\ O
7-(5-ethyl-2-furyl)-3-(3-nitrobenzyl)-3H
145 ~N I ~~
N NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ° .N O
H9C~~H~ ~ ° tent-butyl 6-(5-amino-7-(2-furyl)-3H
146 °~jjT~~ N%' ~ ~ [1,2,3]triazolo[4,5-d]pyrimidine-3-\ N / \ ~N N NHz ylmethyl)indole-1-carboxylate \o 3-(4-amino-3-fluorobenzyl)-7-(2-furyl)-3H-F 'N I N"NH [1,2,3]triazolo[4,5-d]pyrimidine-5-amine HzN I ~ z -\
\ ° tent-butyl (4-(5-amino-7-(2-furyl)-3H
14~ ,.~~° F NN ~ ~ [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-o~° / ~ ~ 3,5-difluorophenyl)carbonate F

\ o 3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-149 N N ~ %N
N
_ ' NH, 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N

HO

F

CHI

\ 0 3-(3-aminobenzyl)-7-(5-ethyl-2-furyl)-3H-N
\

150 ~y ~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~~N
N"NHs l ~

_ I \

3-(3-aminobenzyl)-7-phenyl-3H-N N I /N
N N"NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine HzN
-\
\ O

7-(2-furyl)-3-(6-indolylmethyl)-3H
N

152 I ,I~
~i N NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N

\O

' ~-(2-furyl)-3-(5-indolylmethyl)-3H-N
N

153 ~~
~
~

/ \ N"NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N

-\
\ O

iN
'N 7-(2-furyl)-3-(7-indolylmethyl)-3H-154 I [1,2,3]triazolo 4,5 d midine-5-amine \ '~ N"NHi [ - ]pYri /
N

w \ o 3-(5-fluoro-2-nitrobenzyl)-7-(2-furyl)-3H
~N \N

155 F ~ I ~N~, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine / ~

r \ O

N 3-(2,6-difluoro-4-methoxybenzyl)-7-(2-furyl)-\

156 f 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine F NN N_ 'Nliz ~

/

F

_\
\o N tert-butyl N-(2-(5-amino-7-(2-furyl)-3H
\

~
~
~
N NH

157 z [1,2,3]triazolo[4,5-d]pyrimidine-3-/ ~

N ylmethyl)benzyl)carbamate // O
' CHa O

/
H,C CH, -\
\ O

N 3-(1H-benzotriazol-5-ylmethyl)-7-(2-furyl)-15g N
I 'N
- ' ~ ~

3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NHz N

N

-\
\ 0 7-(2-furyl)-3-(2-methoxy-4-nitrobenzyl)-3H
N

159 ~y' ~ \~~N
"

N [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NHx OzN

OMe -\

N-(3-(5-amino-7-(2-furyl)-3H-160 \ '~N ~ N"NHi [1,2,3]triazolo[4,5-d]pyrimidine-3-o~ ylmethyl)phenylacetamide HOC

-\
\ O

N 3-(2-aminomethylbenzyl)-7-(2-furyl)-3H
\ N

161 ~
~
N"

/ \ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NHz _\

' 3-(3-(N,N-dimethylamino)benzyl)-7-(2-furyl)-N

162 ~ 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~
N;
/ \ N NHi HOC v CHI

_\
\ ~

3-(4-difluoromethoxybenzyl)-7-(2-furyl)-3H-163 N N I '~N
H FF ' N"NHi [1,2,3]triazolo[4,5-d]pyrimidine-5-amine F
O

'-\
\ O

7-(2-furyl)-3-(6-phthalimidomethyl-2-N

~
~ 'N
N"

164 NHs pyridylmethyl)-3H-[1,2,3]triazolo[4,5-/ ~

N d]pyrimidine-5-amine \ o N 3-(3-amino-4-fluorobenzyl)-7-(2-furyl)-3H-,N

N
5 ~
~ N"

NH, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine / \

F
H, \ O
3-(2,3-dihydrobenzofuran-5-ylmethyl)-7-(2-166 N N ~ ~J\ furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-N NHZ

amine \o 3-(5-bromo-2-fluorobenzyl)-7-(2-furyl)-3H
N
N

6r N [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~ ~~
N"NH, 1v F

-\

\ O

N 7-(2-furyl)-3-(2,3,5-trifluorobenzyl)-3H
,N

I
F
~

N"= [1,2,3]triazolo[4,5-d]pyrimidine-5-amine F

-\

\ O

3-(2-fluoro-5-iodobenzyl)-7-(2-furyl)-3H-\
N
N

169 ~
/ ~
N

N- 'NH, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine F

\ O

7-(2-furyl)-3-(2-furylmethyl)-3H-170 N%' ~ ~~N midine-5-amine " [1,2,3]triazolo[4,5-d]pyri N

\a N N I ~ 3-(2-amino-5-fluorobenzyl)-7-(2-furyl)-3H-F
/ \ N NH, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NHs -~
\ o N N tent-butyl (5-(5-amino-7-(2-furyl)-3H-~ N

~
N NHi 172 ~ \ [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-O~N

2-nitrophenyl)carbonate ~CH~
/'CH

~
H,C

-\
~ o 3-(4-amino-3-hydroxybenzyl)-7-(2-furyl)-3H-173 ~N I ~~

N NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine HO

Me -\

3-(4-amino-3-fluorobenzyl)-7-(5-methyl-2-174 ~y'N I ~ furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-N NH

=
/ ~ amine ~N

F

-N

~N ~N 3-(3-aminobenzyl)-7-(1H pyrazol-3-yl)-3H

175 N I ~
N"

NHx [1,2,3]triazolo[4,5-d]pyrimidine-5-amine H,N

_\
\o N 7-(2-furyl)-3-(3-hydroxy-4-nitrobenzyl)-3H-176 I ~N
K

N"NHs [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ozN~

Ho -\
\ o ~N I ,N N-(6-(5-amino-7-(2-furyl)-3H
N~N

177 Hi [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-/ ~

[[JJ N pyridylmethyl)acetamide H,C

O

\ O , N N-(2-(5-amino-7-(2-furyl)-3H
\N

178 N [1,2,3]triazolo[4,5-d]pyrimidin-3-I
/ ~ 'N N~NHi ylmethyl)benzyl)acetamide H;

-\

7-(2-furyl)-3-(3-thienylmethyl)-3H-179 .N \N
I ~ [1,2,3]triazolo[4,5-d)pyrimidine-5-amine N~

a 3-(3-amino-2-methylbenzyl)-7-(5-methyl-2-180 N;N ~ ~~ furyl)-3H-[1,2,3]triazolo[4,5-d]pyrirnidine-5-N

NHZ

~ amine ' HSN
Me -\
O

7-(2-furyl)-3-(3-methyl-2-thienyl)-3H

N~ ~ N [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NH
z s pN ~N 3-(6-allyloxymethyl-2-pyridylmethyl)-N,N-~ I ~ ~~

182 / v diallyl-7-(2-furyl)-3H [1,2,3]triazolo[4,5-~N

o d]pyrimidine-5-amine Me -\

3-(6-methoxymethyl-2-pyridylmethyl)-7-(5-183 N N ~ ~J.. methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-N NHx ' Y
~ -N d]pyrimidine-5-amine Fi, Ma - \

3-(4-aminobenzyl)-7-(5-methyl-2-furyl)-3H

184 ~N ~N
NN ~ ~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NHZ
H
N

z -\
O

N 3-(6-allyloxymethyl-2-pyridylmethyl)-7-(2-~N

~
~
~

185 NHz furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-/ ' N

rN

mine ~

H=C

Me -\

\ O

N 3-(6-allyloxymethyl-2-pyridylmethyl)-7-(5-~N

186 ~ methyl-2-furyl)-3H [1,2,3]triazolo[4,5-I
/ ~ N~NHx ~N d]pyrimidine-5-amine H,6' \ o ~" ~N 7-(2-furyl)-3-(3-isopropyl-4-nitrobenzyl)-3H
I
~

187 , [1,2,3]triazolo[4,5-d]pyrimidine-5-amine / ' N"NH, O,N

Hs ~a -\
\ 0 ~N 7-(2-furyl)-3-(quinolin-2-ylmethyl)-3H-N

~

N"NHZ [1,2,3)triazolo[4,5-d]pyrimidine-5-amine / 'Y
/ 'N

\ O

7-(2-furyl)-3-(4-(N-methylamino)benzyl)-3H

N 5-d]pyrimidine-5-amine I 3]triazolo[4 ~ 2 [1 N , N , NH , z MeNH

'-\
\ o 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-N
190 N I N" d]Pyn~din-3-yl)-1-(6-methyl-2-o NH=

N, ~M8 pyridyl)propanone Me \ N

,,N 3-(3-aminobenzyl)-7-(1H-pyrrol-2-yl)-3H-~N

191 ~
N' N

- 'NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine I v i N

3-(3-nitrobenzyl)-7-(2-pyridyl)-3H
N ~

i "~ I ~

NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /\

o N-(4-(5-amino-7-(2-furyl)-3H
193 0 ~N ~ ~ [1,2,3]triazoloj4,5-d]pyrimidin-3-H,C~( / ~ / ~ ylmethyl)phenyl)acetamide ~\
\ O
'~N ~ ~~ 7-(2-furyl)-3-(4-nitro-2-(2-N NH=
194 ~=N ~ - trimethylsilylethoxy)methoxybenzyl)-3H-a o [1,2,3]triazolo[4,5-d]pyrimidine-5-amine H~c_s;
HsC CHs -\
\ O
~N ~ N 3-(3-ethyl-4-nitrobenzyl)-7-(2-furyl)-3H
195 ~ N"NH
_ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine O=N
CH, -\
O
.,N ~N 7-(2-furyl)-3-(2-(2-thienylethyl))-3H-_ 196 NN I N"NH j1,2,3]triazolo[4,5-d]pyrimidine-5-amine 's ,,N ~N 7-(2-furyl)-3-(6-isopropyl-2-pyridylmethyl)-N I
197 / ~ ~ ~NH= 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 'N
HsC
CH, 7-(2-furyl)-3-(1-(2H-tetrahyropyran-2-198 NN I N~ yl)indazol-5-ylmethyl)-3H-[1,2,3]triazolo[4,5-~N / _ d]pyrimidine-5-amine N
-\
\ ~ 3-(4,6-diisopropyl-2-pyridylmethyl)-7-(2-199 H,C CHa N N I N"NH= furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-> 'Y
-N amine HsC CHa _\
\ o 7-(2-furyl)-3-(5-indazolylmethyl)-3H-N

2OO I ~~
~

N NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine f~

N

N

-\
\ O

N ~ 7-(2-furyl)-3-(2-hydroxy-4-nitrobenzyl)-3H

N
201 i N~N ~ NJ\

~Z [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ozN

off _\
\

N ~-(2-furyl)-3-(6-vinyl-2-pyridylmethyl)-3H-N

202 ~ ~
;
N

NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine / \
~N

H,C

-\
\ O

~ N tent-butyl 5-amino-7-(2-furyl)-3H-N

~

N"NH2 [1,2,3]triazolo[4,5-d]pyrimidine-3-carboxylate H,C
H
CHs ' -\

\ O
tart-butyl 3-(5-amino-7-(2-furyl)-3H

204 "N I ~ [1,2,3]triazolo[4,5-d]pyrimidine-3-~~ ~
~,s H,C O N \
ylmethyl)indole-1-carboxylate _\
\ 6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-205 ~~N I ~J\ d]pyrimidin-3-ylmethyl)pyridine-2-N NH, carboxaldehyde \

tent-butyl 2-(5-amino-7-(2-furyl)-3H-N

~NI
i ~ I

206 ~ \ [1,2,3]triazolo[4,5-d]pyrimidine-3-N NH=

ylmethyl)indole-1-carboxylate kCH, H,C CH, -\
\ O

3-(2-indolylmethyl)-7-(2-furyl)-3H-207 ~ ~~N
~

NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine '-\
~ o 3-(5-ethyl-2-thienylmethyl)-7-(2-furyl)-3H-2O~ iN ~N
I N_ 'Ntiz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine -\
~ o 7-(2-furyl)-3-(3,4-methylenedioxybenzyl)-3H-209 ~;N I
N NH= [1,2,3]triazolo[4,5-d]pyrimidine-5-amine _\
°
,,N ~ ~N 3-(4-amino-3-ethylbenzyl)-7-(2-furyl)-3H
210 / \ ~ N"NHz [1,2,3]triazolo[4,5-d]pyri midine-5-amine HzN
H,C
-\
O
2-(5-amino-7-(2-furyl)-3H-[ 1,2,3] triazolo [4, 5-~N ~ ~ N
211 ° N"NH, d]pyrimidin-3-yl)-1-phenylethanone v/
_\
°
N N ~ ," N-(3-(5-amino-7-(2-furyl)-3H
212 > ~ N NHz [1,2,3]triazolo[4,5-d]pyrimidine-3-~" methyl)phenyl)thiophene-2-carboxamide ;S
-\
° 7-(2-furyl)-3-(6-hydroxymethyl-2-213 N N ~ ~NH pyridylmethyl)-3H-[1,2,3]triazolo[4,5-z d]pyrimidine-5-amine hydrochloride HO
-'\
O
~N ~ .N N-(3-(5-amino-7-(2-furyl)-3H
214 / ~ N NH, [1,2,3]triazolo[4,5-d]pyrimidine-3-H,° ° N methyl)phenyl)-3,3-dimethylbutanamide H~
H,C
-\
O
N-(3-(5-amino-7-(2-furyl)-3H
~N ~ ~ N
215 ~ ~ " "~NH' [1,2,3]triazolo[4,5-d]pyrimidine-3-° ~ methyl)phenyl)cyclopropanecarboxamide -\
\ o ~N ~ ~N 7-(2-furyl)-3-(6-n-propyl-2-pyridylmethyl)-N NHi / \ 3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine 'N

H,C

-\
\ O

N 7-(2-furyl)-3-(6-isobutyloxymethyl-2-~N

~
~
~

217 / ~ pyridylmethyl)-3H-[1,2,3)triazolo[4,5-'~"

~N
d]pyrimidine-5-amine _\

3-(6-bromomethyl-2-pyridylmethyl)-7-(2-21~ NN I N"NH furyl)-3H-[1,2,3]triazolo[4,5-d)pyrimidine-5-z 7- amine ~N

-\

~N ~ ~ N 3-(4-amino-3-isopropylbenzyl)-7-(2-furyl)-219 / \ N"NH2 3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine HSN

H, CHs -\

\ 3-(6-cyanomethyl-2-pyridylmethyl)-7-(2-220 ~N ~ ~NHs furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N

-\

3-(4-hydroxybenzyl)-7-(2-furyl)-3H-N

221 ".
t ,~N 1 l idi i ri N"NH, [
-am , , ]triazo ne-ne o 4 d m [ , - )py Ho -\

~N I ~ 2-(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-'' N NH

d]pyrimidin-3-yl)-1-(4-nitrophenyl)ethanone /

~
OiN

-\
\ o I ~ 4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-223 O N NH=
d]pyrimidin-3-ylacetyl)-benzonitrile NC

-\
\ O

N N ~ .N N-(3-(5-amino-7-(2-furyl)-3H-' N~NN

224 z [1,2,3]triazolo[4,5-d]pyrimidin-3-/ \

o-,N ylmethyl)phenyl)propanesulphonamide -\
\ ~

-' ' N-(3-(5-amino-7-(2-furyl)-3H-NN ~ N"NHs [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-5-chloro-2-a thiophenesulphonamide -v \ o 7-(2-furyl)-3-(6-(N-methylamino)methyl-2-N
~

N
226 ~ pyridylmethyl)-3H-[1,2,3]triazolo[4,5-N
\N N"NHZ

d]pyrimidine-5-amine hydrochloride H,C

-\
\ 0 N 2-(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-~N

N
I
' " 'N"

227 d]pyrimidin-3-yl)-1-(4-(N,N-diethylamino)phenyl)ethanone H,C~N~CH~

-\
\ O

N ~ 7-(2-furyl)-3-(6-isopropyl-3-pyridylmethyl)-N
i 3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine H,o \ o N 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-~N

I
- ' ~

229 NH2 d]pyrimidin-3-yl)-1-(4-N

methoxyphenyl)ethanone \ /

Me0 -\
\ O

N tent-butyl 7-(5-amino-7-(2-furyl)-3H-~ N

230 I [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-' / \ \ N~NH2 - N 5-chloroindole-1-carboxylate ~ CH

W
I
O--~-CH' CH' -\
\ O

.,N 3-(5-chloro-7-indolyl)-7-(2-furyl)-3H
~N

231 ~
ci ~ N- ' NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /~
N

\ O

N-(3-(5-amino-7-(2-furyl)-3H

N
[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-3,5-dimethylisoxazol-4-,~ -WN ylsulphonamide N

-\
\ O

N N I ~N 3-(6-(N,N-dimethylamino)methyl-2-" H
\

233 NHs -N pyridylmethyl)-7-(2-furyl)-3 ~

/ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine -Y

HOC
r -\
\ O

7-(2-furyl)-3-(6-methylthiomethyl-2-NN I ~N
234 ~ ~~NH, pyridylmethyl)-3H-[1,2,3]triazolo[4,5-/ -Y d]pyrimidine-5-amine H,C

-\

N ~N 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-235 N~ I N~NH

O
2 d]pyrimidin-3-yl)-1-(2-nitrophenyl)ethanone NOx -\

N-(3-(5-amino-7-(2-furyl)-3H-N

N
I ~N

N"NHz [1,2,3]triazolo[4,5-d]pyrimidin-3-o ylmethyl)phenyl)-1,2-dimethyl-1H-imidazol-o=S-~ 4-ylsulphonamide N
HaC~

~s \ 0 N,N-bis(6-(5-amino-7-(2-furyl)-3H

rimidin-3- lmeth 1 -2-237 \ ~ ' ~ ~ ~ I [1,2,3]triazolo[4,5-d]py y Y
w ) pyridylmethyl) methanesulphonamide 7-(2-furyl)-3-(6-methylsulphonylmethyl-2-N
I
~

238 \ pyridylmethyl)-3H [1,2,3]triazolo[4,5-N
N
r~

d]pyrimidine-5-amine \\

o=s ~c -\

N-(6-(5-amino-7-(2-furyl)-3H

~N ~ ~~ [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-Y pyridylmethyl)-N-methyl ~N

HsC
methanesulphonamide HoO~~ O

O

H3C, .CH, ~\( /

N 3_(3-aminobenzyl)-7-(4,5-dimethyl-2-~
S

240 NN ~ e~N thiazolyl)-3H [1,2,3]triazolo[4,5-N"
H

z N d]pyrimidine-5-amine HsN

-\
~ o 3-(4-amino-2-fluorobenzyl)-7-(2-furyl)-3H
241 N ~
N N r~-~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /~
F
-\
O
2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-indanone -\

243 N N ~ ~NI 7-(2-furyl)-3-(5-methyl-7-indolylmethyl)-3H
H30 \N N NHz [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /v N
-\
O
N-(4-(5-amino-7-(2-furyl)-3H
244 0 "N ~ N~~ [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-H~N ~' methylphenyl)formamide -\
~N ~N 2-(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-245 O N' ~ N~NFis d]pyrimidin-3-yl)-1-phenylpropanone CH, -\
O
3-(7-fluoro-5-indolyl)-7-(2-furyl)-3H

N NHz (1,2,3]triazolo[4,5-d]pyrimidine-5-amine N
-\
~ o 7-(2-furyl)-3-(6-isopropoxymethyl-2-NN I ~N
247 / ~ ~ N'~~ pyridylmethyl)-3H-[1,2,3]triazolo[4,5 ~N d]pyrimidine-5-amine CH, ° 3-(6-ethyl-2-pyridylmethyl)-7-(5-methyl-2-248 N N ~ ~~N furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-N_ 'NH2 ~~ amine HOC
-\
O
,,N ~N 3-(4-chloro-5-indolyl)-7-(2-furyl)-3H
249 N~N I
N NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /~
N
ci -\

3-{7-bromo-5-indolyl)-7-(2-furyl)-3H
25~ 8r N N I
N NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /v N
O
3-(6-chloro-5-indolyl)-7-(2-furyl)-3H
iN 'NI
251 C~ NON I N~~z [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /~
N
3-(3-(4-fluorobenzylamino)benzyl)-7-(2-252 ~ / ~N ~ '~ furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-N N
/ ~ ~ amine 3-(6-ethoxy-2-pyridylmethyl)-7-(2-furyl)-3H-253 ~ N NH, [1,2,3]triazolo[4,5-d]pyrimidine-5-amine ~N
O
H
CHI
-\
O
3-(6-ethoxy-2-pyridylmethyl)-7-(5-methyl-2 254 N I ~~ fur 1 -3H- 1,2,3]triazolo 4 5 d rimidine-5 N NHZ y ) [ [ ~ - ]py j 'Y
_N amine H,c 3-(3-(2-pyridylmethylamino)benzyl)-7-(2-255 ~ / NN ~ ~N furyl)-3H-[1,2,3]triazolo[~.,5-d]pyrimidine-5-N N 'N
N "~ amine /~
° 7-(2-furyl)-3-(1-(4-256 N N I ~ trifluoromethylphenyl)ethyl)-3H
/ \ N N NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine cFg~~
-\

.,N I ~N 3-(6-fluoro-5-indolyl)-7-(2-furyl)-3H
257 F N'N N"NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine / ~
N, ~ o 3-(5-fluoro-2-indolyl)-7-(2-furyl)-3H-N N r~ [1,2,3]triazolo[4,5-d]pyrimidine-S-amine F a N
-\

N N I ,N 3-(3,5-dimethyl-4-nitrobenzyl)-7-(2-furyl)-259 H~~ ' N"NHs 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine OzN
HsC
O
3-( 1-(3-fluorophenyl)ethyl)-7-(2-furyl)-3H-pN ~ N
260 N N I N~NHZ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine /~
~~s ~''F
-\
O
3-(7-chloro-S-indolyl)-7-(2-furyl)-3H
iN ~N
261 °, N' I N~NH2 [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N
U

-\
\ o ,,N ~N 3-(4-amino-3,5-dimethylbenzyl)-7-(2-furyl)-~

,~C 3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NI-l~
N
l~

HzN

-\
\ O

,,N 3-(1-(3-aminophenyl)ethyl)-7-(2-furyl)-3H
~N

263 I [1,2,3]triazolo[4,5-d]pyrimidine-5-amine NON N~~2 l \ CH9 FilN

-\
O

N 7-(2-furyl)-3-(6-(2-methoxyethyl)-2-~N

264 N pyridylmethyl)-3H-[1,2,3]triazolo[4,5-I
~ ~NH=
~ ' Y
-N d]pyrimidine-5-amine HsC~O

-\
' ~

7-(2-furyl)-3-(1-(5,6-dimethyl-2-265 r',~ I ~ pyridyl)propyl)-3H [1,2,3]triazolo[4,5-~

d]pyrimidine-5-amine N
H

HOC

-N

\ N
3-(3-nitrobenzyl)-7-(1H pyrazol-3-yl)-3H

266 N N I N"NH [1,2,3]triazolo[4,5-d]pyrimidine-5-amine Z

l ~ hydrochloride Me -\

' 7-(5-methyl-2-furyl)-3-(2-methyl-3-267 N N I ~~ nitrobenzyl)-3H-[1,2,3]triazolo[4,5-N

N ~

l \ d]pyrimidine-5-amine ' Me Me -\

\ 7-(5-methyl-2-furyl)-3-(4-nitrobenzyl)-3H-N N I ~ [1,2,3]triazolo[4,5-d]pyrimidine-5-amine N NH

i N

-\

tart-butyl N-(4-(5-amino-7-(2-furyl)-3H

269 NN I ~ [1,2,3]triazolo[4,5-d]pyrimidine-3-o-~ , oJ( / ~ N ylmethyl)phenyl)-N-methylcarbamate f , o cH, ~ l "' 3H
\ N1 ~ )-~ -tart-butyl 2-(5-amino-3-(3-nitrobenzy 270 N N I N~ [1,2,3]triazolo[4,5-d]pyrimidin-7-yl)pyrrole-1-N~

/ ~ carboxylate ' OZN

Me Me N~ S 7_(4,5-dimethylthiazol-2-yl)-3-(3-271 N N I ~ nitrobenzyl)-3H-[1,2,3]triazolo[4,5-/ \ N N NH2 d]pyrimidine-5-amine _\
\ O

3-(2-fluoro-4-nitrobenzyl)-7-(2-furyl)-3H
N

I

[1,2,3]triazolo[4,5-d]pyrimidine-5-amine o~N

F

-\
\ 0 N tart-butyl 7-(5-amino-7-(2-furyl)-3H-, N

N
I
~
\
"'e 273 NHz [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-N
/ \

' N 5-methylindole-1-carboxylate ~ CH

w 0--~CH9 CHI

-\
O

ethyl N-(4-(5-amino-7-(2-furyl)-3H-274 '~~N~ [1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)-~
~~'o~ /

N , 2-methylphenyl)carbamate Me The general synthetic methods used for the preparation of these Examples are set out below as Methods A to BH. Table 2 sets out the Method used for each Example, together with analytical data.
HPLC is carned out using the following conditions: Column. Waters Xterra RP 18 (50 x 4.6 mm); Particle size 5 ~.M; Mobile phase MeOH: 10 mM aq NHa.OAc (pH 7 buffer);
Gradient 50:50 isocratic for 1 min. then linear gradient 50:50 to 80:20 over 5 min. then 80:20 isocratic for 3 min.; Flow rate 2.0 mL/min.; Detection wavelength ~, =
230 nM.
Retention times are provided.
Method A
7-(2-Furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 1) A solution of 7-chloro-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-anune (570 mg, 3.34 mmol) in N-methyl-2-pyrrolidinone (4 mL) was treated with PdCl2(PPh3)~ (117 mg, 0.17 mmol) and 2-(tributylstannyl)furan (1.05 mL, 1 mmol), stirred at 80 °C for 5 h, diluted with EtOAc, filtered through a silica pad and concentrated in vacuo. The residue was triturated with diethyl ether and the title compound isolated as a yellow solid (438 mg, 65 %).
Method B
3-(2-Fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 3) A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (101 mg, 0.5 mmol) in DMF (2 mL), at 0 °C, was treated with NaH (20 mg, 60 %, 0.5 mmol), stirred for 20 rains then treated with 2-fluorobenzyl bromide (60 ~,L, 0.5 mmol). The reaction mixture was allowed to warm to room temperature, stirred for 1 h, quenched with water, extracted with EtOAc, dried (MgS04) and concentrated in vacuo. The crude product was purified by chromatography (EtOAc : Heptane, 1:4 - EtOAc : Heptane, 2:1) to give N,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-(2-furyl)-3H [1,2,3]triazolo[4,5-d]pyrimidine-5-anune (Example 2) (28 mg, 11 %) as a yellow solid and the title compound (34 mg, 22 %) as a yellow solid.

Method C
3-(3-Ariiinobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 5) A solution of 7-(2-furyl)-3-(3-nitrobenzyl)-3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine (152 mg, 0.45 mmol) in EtOH (2 mL) at 50 °C was treated with a solution of SnCl2 (305 mg, 1.35 mmol) in conc. HCl (0.7 mL), stirred for 2 h, cooled, diluted with water, basified to pH 10 (5-M, NaOH) and filtered to give the title~compound (127 mg, 92 %) as a white solid.
Method D
N-(3-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)phenyl-(1-methyl-1H-imidazol-4-yl)sulphonamide (Example 9) A solution of 3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (125 mg, 0.41 mmol) in DMF (2 mL) was treated with Et3N (85 ~.L, 0.61 mmol) and 1 methylimidazole-4-sulphonyl chloride (74 mg, 0.41 mmol), stirred at room temperature overnight, poured into water, extracted with EtOAc, dried (MgS04) and concentrated in vacuo. The crude product was purified by chromatography [Si02; EtOAc : MeOH
(1:10)]
to give the title compound (26 mg, 14 %) as a cream solid.
Method E
5-Amino-N-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylcarboxamide (Example 10) A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (202 mg, 1.0 mmol) in DMF (3 mL) was treated with benzyl isocyanate (123 p.L, 1.0 mmol) and a catalytic amount of DMAP, stirred at room temperature overnight, diluted with EtOAc and filtered to give the title compound (62 mg, 19 %) as a peach coloured solid.
Method F
Ethyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate (Example 14) A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (101 mg, 0.5 mmol) in DMF (4 mL) was treated with 4-(N,N-dimethylamino)pyridine (5 mg, 0.04 mmol) and ethyl bromoacetate (55 ~.L, 0.5 mmol), stirred at room temperature for 16 h and purified directly by chromatography [Si02; EtOAc : Heptane (1:2)] to give the title compound (50 mg, 35 %) as a white solid.
Method G
7-(2-Furyl)-3-(3-hydroxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 18) A solution of 7-(2-furyl)-3-(3-methoxybenzyl)-3H [1,2,3]triazolo[4;5-d]pyrimidine-5-amine (119 mg, 0.37 mmol) in dichloromethane (20 mL) at 0 °C was treated with boron tribromide (1-M in dichloromethane, 8.8 mL, 8.8 rnmol) portion-wise over 3 days, concentrated in vacuo and isolated by filtration to give the title compound (114 mg, 100 %) as a yellow solid.
Method H
6-(5-Methyl-2-furyl)-5-nitropyrimidine-2,4-diamine A solution of 6-chloro-5-nitropyrimidine-2,4-diamine (10 g, 60 % pure, 32 mmol) in THF
(300 mL) was treated with saturated aq NaHC03 (75 mL), 5-methylfuran-2-boronic acid (7.33 g, 0.058 mol) and Pd(PPh3)4 (1 g, 0.865 mmol) and refluxed with vigorous stirring under argon overnight. The mixture was cooled to room temperature, diluted with EtOAc (400 mL) and water (300 mL), filtered to remove insoluble material and the filtrate was extracted with EtOAc (2 x 100 mL). The combined organic phase was dried (MgS04), concentrated in vacuo and the resulting solid triturated with dichloromethane and filtered to give the title compound (6 g, 72 %) as a yellow solid; mp 196.3 - 196.9 °C; IR v,~,~
(Nujol)/crri 1 3442, 3169, 2930, 1629, 1463, 1377, 1027, and 790; NMR 8H (400 MHz, I~MSO) 7.40 (2H, br s), 7.09 (2H, br s), 6.87 (1H, dd, J 0.5, 3.2 Hz), 6.26 (2H, dd, J 1.0, 3.3 Hz) and 2.28 (3H, s).
Method I
6-(5-Methyl-2-furyl)pyrimidine-2,4,5-triamine A suspension of 6-(5-methyl-2-furyl)-5-nitropyrimidine-2,4-diamine (6.6 g, 29.6 mmol) and 10 % Pd/C (0.66 g) in MeOH (100 mL) was heated at 40 °C under an atmosphere of Ha for 3 h, cooled to room temperature, filtered through Celite, and concentrated in vacuo to give the title cornpound (5.8 g, 99 %) as an off-white solid; 1R vmaX
(DR)lcrri 1 3333, 2237, 1634, 1458, 1237, 1025, 963 and 828; NMR SH (400 MHz, DMSO) 6.77 (1H, dd, J
0.5, 3.2 Hz), 6.21- 6.17 (3H, m), 5.14 (2H, s), 4.21 (2H, s), and 2.35 (3H, s).
Method J
7-(5-Methyl-2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 19) A solution of 6-(5-methyl-2-furyl)pyrimidine-2,4,5-triamine (5.8 g, 30.1 mmol) in dioxane (116 mL) was treated with isoamyl nitrite (4.1 mL, 30.5 mmol), heated at 80 °C for 3.5 h, cooled to room temperature and the resulting precipitate was filtered, washed with dioxane (10 mL) and heptane (2 x 15 mL) then triturated with heptane and filtered to give the title compound (4.7 g, 77 %) as a sandy solid.
Method I~
7-(1H-Pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 21) A solution of 7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (120 mg, 0.361 mmol) in MeOH (2 mL) was treated with HCl (4-M in dioxan, 1 mL), stirred for 2 h, filtered and the resulting solid washed with Et20 to give the title compound (76 mg, 100 %) as a yellow solid.
Method L
(2-Amino-6-(2-furyl)-5-nitropyrimidin-4-yl) 4-methylbenzenesulphonate A suspension of 2-amino-6-(2-furyl)-5-nitropyrimidine-4(1H)-one (1.00 g, 4.50 mmol) in dichloromethane (50 mL) was treated with triethylamine (0.941 mL, 6.75 mmol) and p toluenesulfonyl chloride (944 mg, 4.95 mmol), stirred for 1 h, diluted with dichloromethane (50 mL), washed with 2-M HCl (20 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography [SiO2; isohexane:EtOAc (2:1)] to give the title compound (410 mg, 24 %) as a yellow solid; NMR 8H (400 MHz, CDCl3) 7.95 (2H, d, J
8.5 Hz), 7.59-7.57 (1H, m), 7.39 (2H, d, J 8.5 Hz), 7.23-7.21 (1H, m), 6.59-6.51 (1H, m), 5.39 (2H, br s), 2.48 (3H, s); Retention time 5.68 min.

Method M
6-(2-Furyl)-5-vitro-N4-(2-pyridylmethyl)pyrimidine-2,4-diamine A solution of (2-amino-6-(2-furyl)-5-nitropyrimidin-4-yl) 4-methylbenzenesulphonate (478 mg, 1.27 mmol) in dimethoxyethane (15 mL) was treated with triethylamine (0.531 5 mL, 3.81 mmol) and 2-pyridinemethylamine (0.393 mL, 3.81 mmol), stirred for 16 h, poured into water (100 mL) and the resulting solid was filtered to give the title compound (275 mg, 69 %) as a yellow solid; NMR ~H (400 MHz, CDCl3) 8.70 - 8.58 (2H, m), 7.70 7.66 (1H, m), 7.55 - 7.54 (1H, m), 7.28 (1H, d, J 8.0 Hz), 7.24 - 7.20 (1H, m), 7.07 - 7.06 (1H, m), 6.54 - 6.52 (1H, m), 5.26 (2H, br s) and 4.83 (2H, d, J 5.0 Hz);
Retention time 10 1.44 min.
Method N
7-(2-Furyl)-3-(2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 24) 15 A solution of 6-(2-furyl)-5-vitro-N4-(2-pyridylmethyl)pyrimidine-2,4-diamine (270 mg, 0.864 mmol) and 10 % Pd/C (92 mg, 0.086 mmol) in EtOH (30 mL) and EtOAc (10 mL) was stirred under an hydrogen atmosphere for 1 h, filtered through Celite and concentrated in vacuo. The resulting yellow oil was dissolved in in dioxane (25 mL), treated with isoamyl nitrite (0.109 mL, 0.815 mmol), stirred at 100 °C for 6 h, cooled to room 20 temperature, filtered through Celite, concentrated in vacuo and triturated with Et20 to give the title compound (110 mg, 46 %) as a yellow solid.
Method O
(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid (Example 26) 25 A solution of ethyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate (547 mg, 1.89 mmol) in MeOH (5 mL) was treated with aqueous NaOH (2 mL, 2-M, 4 mmol), refluxed for 10 min, cooled, acidified with aqueous HCl (1-M), filtered and dried to give the title compound (417 mg, 85 %) as a white solid.

30 Method P
(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(3-chlorophenyl)acetamide (Example 31) A suspension of (5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid (140 mg, 0.5 mmol) in DMF (1 mL) was treated with carbonyl diimidazole (81 mg, 0.5 mrnol), stirred at room temperature for 1 h, treated with 3-chloroaniline (53 ~L,, 0.5 mmol) and the mixture heated to 50 °C for 16 h. The reaction mixture was cooled, diluted with water (3 mL) and filtered to give the title compound (94 mg, 48 %) as a cream solid.
Method Q
3-(2-Fluorobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 34) A stirred solution of thiazole (0.10 mL, 1.43 mmol) in dry THF (5 mL) at -78 °C, under argon was treated with n-BuLi (0.9 mL, 1.6-M in hexanes, 1.43 mmol), stirred for 30 min, treated with a solution of ZnCh (1.8 mL, 1-M in Et2O, 1.80 mmol) and allowed to warm gradually to room temperature. The mixture was treated with 7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (200 mg, 0.714 mmol) and Pd(PPh3)4 (50 mg), refluxed for 2 h and partitioned between saturated NH4C1 (20 mL) and EtOAc (20 mL). The organic phase was dried (MgS04), concentrated in vacuo and purified by chromatography [Si02; iso-hexane : EtOAc (1:1)] to give the title compound (70 mg, 30 %) as a cream solid.
Method R
N-(2-Amino-6-(2-furyl)-5-nitropyrimidine-4-yl)-6-chloropyridine-3-carboxamide A solution of 6-(2-furyl)-5-nitropyrimidine-2,4-diamine (500 mg, 2.26 mmol) in pyridine (10 mL) was treated with 6-chloronicotinoyl chloride (438 mg, 2.49 mmol), stirred for 16 h at 80 °C, cooled to room temperature, poured into water (100 mL) and extracted with EtOAc (2 x 25 mL) and the combined organic phase was dried (MgS04), concentrated in vacuo and purified by chromatography [Si02; isohexane:EtOAc (3:2)] to give the title compound (430 mg, 82 %) as a yellow solid; NMR 8H (400 MHz, DMSO) 11.14 (1H, s), 8.86 (1H, d, J 2.5 Hz), 8.27 (1H, dd, J 8.5, 2.5 Hz), 7.93 (1H, m), 7.77 (2H, br s), 7.65 (1H, d, J 7.5 Hz), 7.09 (1H, d, J 4.5 Hz), 6.72 - 6.70 (1H, m); Retention time 2.41 min.
Method T
6-Chloro-N-(7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)pyridine-3-carboxamide (Example 44) A solution of N-(2-amino-6-(2-furyl)-5-nitropyrimidine-4-yl)-6-chloropyridine-carboxamide (153 mg, 0.423 mmol) and 10% Pd/C (82 mg, 42.3 pmol) in EtOH (20 mL) and EtOAc (5 mL) was stirred under an hydrogen atmosphere for 3 h, filtered through Celite and concentrated in vacuo to give N-(2,5-diamino-6-(2-furyl)pyrimidin-4-yl)-6-chloropyridine-3-carboxamide as a yellow oil. A solution of this product in EtOH (5 mL) and 2-M HCl (5 mL) at 0 °C was treated dropwise with an ice-cold solution of sodium nitrite (87 mg, 1.27 mmol) in water (2 mL). The mixture was stirred at 0 °C for 1 h, stirred at room temperature for 1 h, neutralised with 5-M NaOH, stirred for 16 h and the resulting solid was filtered to give title compound (40 mg, 28 %) as a brown solid.
Method U
6-Chloro-N4-(3-nitrobenzyl)pyrimidine-2,4,5-triamine A mixture of 4,6-dichloropyrimidine-2,5-diamine (700 mg, 3.91 mmol), 3-nitrobenzylamine hydrochloride (885 mg, 4.69 mmol) and triethylamine (1.6 mL, 11.7 mmol) in n-BuOH (20 mL) was refluxed for 17 h, concentrated in vacuo and the residue partitioned between EtOAc (10 mL) and H20 (5 mL). The organic phase was dried (MgSO4) and concentrated in vacuo to give the title compouhd as an orange solid (906 mg, 76 %) which was used in the next reaction without further purification; NMR 8H
(400 MHz, CDC13) 8.16 (1H, s), 8.10 (1H, d, J 8.0 Hz), 7.80 (1H, d, J 7.5 Hz), 7.62 (1H, t, J 7.5 Hz), 7.25 (1H, t, J 6.0 Hz), 5.69 (2H, s), 4.67 (2H, d, J 6.0 Hz) and 3.93 (2H, br s).
Method V
3-Chloromethyl-N,N-dimethylbenzamide A solution of 3-(chloromethyl)benzoyl chloride (426 ~I,, 3 mmol) and Et3N (626 ~t.L, 4.5 mmol) in THF (5 mL) was treated with dimethylamine (1.5 mL, 2-M in THF, 3 mmol), stirred at room temperature for 1 h, poured into water, extracted with EtOAc, dried (MgS04) and concentrated in vacuo to give the title compound (580 mg, 98 %) as a colourless oil; NMR 8H (400 MHz, CDCl3) 7.46 - 7.34 (4H, m), 4.59 (2H, s), 3.11 (3H, s) and 2.98 (3H, s); Anal. Calcd for CIaHI~N6O2 ~ 0.2 HZO: C, 49.38; H, 4.28, N, 28.79.
Found: C, 49.25; H, 4.09; N, 28.47.
Method W

7-(2-Furyl)-3-(2-methoxy-5-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 66) A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (606 mg, 3 mmol) in DMF (5 mL) at 0 °C, was treated with CsC03 (977 mg, 3 mmol), stirred fox 1 h, treated with 2-methoxy-5-nitrobenzyl bromide (738 mg, 3 mmol) and stirred at room temperature for 1 h. The reaction mixture was diluted with water (10 mL), filtered and the resulting solid purified by chromatography [SiOa; EtOAc : Heptane (2:1)] to give the title compouyad (279 mg, 25 %) as a yellow solid.
Method X
3-(2-Fluorobenzyl)-7-(5-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 69) A stirred solution of oxazole (138 mg, 2.0 mmol) in dry THF (10 mL) at -78 °C, under argon was treated with n-BuLi (1.25 mL, 1.6-M in hexanes, 2.0 mmol), stirred for 30 min, treated with a solution of ZnCl2 (2.0 mL, 1-M in Et2O, 2.0 mmol)) and allowed to warm gradually to room temperature. The mixture was treated with 7-chloro-3-(2-fluorobenzyl)-3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine (280 mg, 1.0 mmol) and Pd(PPh3)4 (100 mg), refluxed for 4 h and partitioned between saturated NH~Cl solution (10 mL) and EtOAc (10 mL). The organic phase was dried (MgSO4), concentrated in vacuo and purified by .
chromatography [Si02; iso-hexane : EtOAc (1:1), then neat EtOAc] to give the title compound (6 mg, 2 %) as a beige solid.
Method ~
3-(2-Fluorobenzyl)-7-(1H-triazol-4-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 80) A mixture of 7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (145 mg, 0.50 mmol), tributyl 1-(2-(trimethylsilyl)ethoxymethyl)-1H triazol-5-ylstannane (336 mg, 0.75 mmol) and Pd(PPh3)2C12 (35 mg, 0.05 mmol) in DMF (2 mL) was shaken at 80 °C for 17 h then purified directly by chromatography [5102; iso-hexane : EtOAc (2:1)]
to give 3-(2-fluorobenzyl)-7-(1-(2-trimethylsilyl)ethoxymethyl)-1H triazol-5-yl)-3H
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine as a colourless oil. This material was dissolved in MeOH (1 mL), treated with a solution of HCl (0.5 mL, 4-M in dioxane), stirred for 17 h, concentrated in vacuo and the residue triturated with Et20 to give the title compound (16 mg, 10 %) as an off white solid.
Method Z
3-(4-Hydroxylamino-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 87) A solution of .7-(5-methyl-2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (60 mg, 0.17 mmol) in EtOH (40 mL), MeOH (20 mL) and water (15 mL) was treated with ammonium chloride (280 mg, 5.23 mmol) and zinc (138 mg, 2.05 mmol), stirred for 1 h, filtered through Celite, concentrated irz vacuo to ~20 mL, diluted with brine (20 mL), extracted with EtOAc (3 x 20 mL) and the combined organic phase dried (MgS04) and concentrated irz vacuo to give the title compound (40 mg, 73 %) as a yellow solid.
Method AA
3-(3-Aminomethylbenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (example 101) A stirred solution of the , 7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-1H
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (330 mg, 1 mmol) in dry DMF (5 mL) was treated with NaH (40 mg, 60 % in oil, 1 mmol), stirred for 15 min, treated with tart-butyl N-(3-(bromomethyl)benzyl)carbamate (300 mg, 1 mmol) and stirred for 1 h. The mixture was partitioned between EtOAc (20 mL) and HBO (20 mL), the organic phase was dried (MgS04), concentrated in vacuo and purified by chromatography [Si02; iso-hexane EtOAc (1:1)]., The resulting yellow syrup was dissolved in MeOH (3 mL), treated with HCl (2 mL, 4-M in dioxane), stirred for 17 h and the resulting solid filtered to give the title compound (258 mg, 80 %) as a cream solid.
Method AB
2-Bromomethyl-6-(methoxymethyl)pyridine A solution of 6-methoxymethyl-2-pyridinemethanol (860 mg, 5.64 mmol) and triphenylphosphine (1.78 g, 6.77 mmol) in dichloromethane (40 mL) at 0 °C was treated portionwise with CBr4 (2.80 g, 8.43 mmol), stirred for 1. h, concentrated irz vacuo and purified by chromatography [SiO2; isohexane:EtOAc (3:1)] to give the title compound (1.20 g, 99 %) as a colourless oil; NMR 8H (400 MHz, CDC13) 7.71 (1H, t, J 8.0 Hz), 7.35 (2H, d, J 8.0 Hz), 4.58 (2H, s) and 4.54 (2H, s).
The following novel compounds were also synthesised by Method AB fxom the 5 appropriate alcohol.
2-Bromomethyl-4-methylpyridine NMR ~H (400 MHz, CDCl3) 8.43 (1H, d, J 5.0 Hz), 7.26 - 7.25 (1H, m), 7.03 (1H, d, J 5.0 Hz), 4.51 (2H, s) and 2.36 (3H, s).
2-Bromomethyl-6-ethylpyridine NMR ~H (400 MHz, CDCl3) 7.60 (1H, t, J 7.5 Hz), 7.26 (1H, d, J 7.5 Hz), 7.08 (1H, d, J
7.5 Hz), 4.53 (2H, s), 2.82 (2H, q, J 7.5 Hz) and 1.30 (3H, t, J 7.5 Hz).
4-Bromomethyl-2-ethylpyridine NMR 8H (400 MHz, CDCl3) 8.51 (1H, d, J 5.0-Hz), 7.17 - 7.16 (1H, m), 7.13 -7.11 (1H, m), 4.37 (2H, s), 2.84 (2H, q, J 7.5 Hz) and 1.32 (3H, t, J 7.5 Hz).
tart-Butyl (4-bromomethyl-3,5-difluorophenyl) carbonate NMR bH (400 MHz, CDC13) 6.80 (2H, m), 4.49 (2H, s) and 1.56 (9H, s).
2-Fluoro-5-iodobenzyl bromide NMR 8H (400 MHz, DMSO) 7.94 - 7.91 (1H, dd, J 2.5, 7.5 Hz), 7.76 - 7.71 (1H, m), 7.12 -7.06 (1H, dd, J 8.5, 10.0 Hz) and 4.66 - 4.64 (2H, s).
2-Allyloxymethyl-6-bromomethylpyridine NMR 8H (400 MHz, CDCl3) 7.71 (1H, t, J 7.5 Hz), 7.40 (1H, d, J 7.5 Hz), 7.34 (1H, d, J
7.5 Hz), 6.03 - 5.93 (1H, m), 5.37 - 5.32 (1H, m), 5.26 - 5.22 (1H, m), 4.64 (2H, s), 4.54 (2H, s) and 4.14 - 4.12 (2H, m).
4-Nitro-2-(2-trimethylsilylethoxy)methoxybenzyl bromide NMR 8H (400 MHz, CDCl3) 7.99 (1H, d, J 2.0 Hz), 7.84 (1H, dd, J 8.4, 2.0 Hz), 7.49 (1H, d, J 8.4 Hz), 5.41 (2H, s), 4.55 (2H, s), 3.82 (2H, m), 0.96 (2H, m) and 0.01 (9H, s).

2-Bromomethyl-4,6-diisopropylpyridine NMR bH (400 MHz, CDC13) 7.12 (1H, s), 6.93 (1H, s), 4.52 (2H, s), 3.03 (1H, sept, J 7.0 Hz), 2.87 (1H, sept, J 7.0 Hz), 1.29 (6H, d, J 7.0 Hz) and 1.25 (6H, d, J 7.0 Hz).
2-Bromomethyl-6-isopropylpyridine NMR SH (400 MHz, CDCl3) 7.63 - 7.59 (1H, m), 7.27 - 7.25 (1H, m), 7.10 - 7.08 (1H, rn), 4.54 (2H, s), 3.06 (1H, sept, J 7.0 Hz) and 1.30 (6H, d, J 7.0 Hz).
2-Bromomethyl-6-vinylpyridine NMR 8H (400 MHz, CDC13) 7.66 (1H, t, J 7.5 Hz), 7.34 - 7.28 (2H, m), 6.81 (1H, dd, J
10.5, 17.5 Hz), 6.22 (1H, dd, J 1.0, 17.5 Hz), 5.51 (1H, dd, J 1.0, 10.5 Hz) and 4.55 (2H, s).
2-Bromomethyl-5-ethylthiophene NMR SH (400 MHz, DMSO) 6.85 - 6.82 (1H, d, J 3.5 Hz), 6.71 - 6.68 (1H, d, J
3.5 Hz), 4.59 - 4.55 (2H, s), 2.81 - 2.75 (2H, m) and 1.25 - 1.20 (3H, m).
2-Bromomethyl-6-n-propylpyridine NMR 8H (400 MHz, CDC13) 7.59 (1H, t, J 7.5 Hz), 7.26 (1H, d, J 7.5 Hz), 7.06 (1H, d, J
7.5 Hz), 4.53 (2H, s), 2.76 (2H, t, J 7.5 Hz), 1.74 (2H, sext, J 7.5 Hz) and 0.97 (3H, t, J 7.5 Hz).
2-Bromomethyl-6-isobutyloxymethylpyridine NMR ~H (400 MHz, CDC13) 7.71 (1H, t, J 7.5 Hz), 7.41 (1H, d, J 7.5 Hz), 7.33 (1H, d, J
7.5 Hz), 4.62 (2H, s), 4.53 (2H, s), 3.33 (2H, d, J 6.5 Hz), 1.91 - 2.01 (1H, m) and 0.96 (6H, d, J 6.5 Hz).
5-Bromomethyl-2-isopropylpyridine NMR bH (400 MHz, CDC13) 8.54 (1H, m), 7.65 (1H, dd, J 2.5, 8.0 Hz), 7.16 (1H, d, J 8.0 Hz), 4.47 (2H, s), 3.07 (1H, sept, J 7.0 Hz) and 1.30 (6H, d, J 7.0 Hz).
2-Bromomethyl-6-isopropyloxymethylpyridine NMR 8H (400 MHz, CDC13) 7.71 - 7.67 (1H, m), 7.42 - 7.40 (1H, m), 7.33 - 7.31 (1H, m), 4.63 (2H, s), 4.53 (2H, s), 3.75 (1H, sept, J 6.0 Hz) and 1.25 (6H, d, J 6.0 Hz).
Method AC
S 2-Bromomethyl-4-nitropyridine A solution of 2-methyl-4-nitropyridine (1.79 g, 13.0 mmol) in CCl4 (30 mL) was treated with N bromosuccinimide (2.31 g, 13.0 mmol) and benzoyl peroxide (420 mg, 1.30 mmol), stirred at 80 °C for 16 h, cooled to room temperature, filtered through Celite, concentrated in vacuo and purified by chromatography [Si02; isohexane:EtOAc (15:1)] to give the title compound (700 mg, 25 %) as a colourless oil; NMR 8H (400 MHz, CDC13) 8.89 (1H, d, J
5.0 Hz), 8.19 (1H, d, J 2.0 Hz), 7.96 (1H, dd, J 5.0, 2.0 Hz) and 4.66 (2H, s).
The following novel compounds were also synthesised by bromination of the appropriate arylallcyl compounds using Method AC.
2-Bromomethyl-6-methyl-4-nitropyridine NMR ~H (400 MHz, CDCl3) 7.99 - 7.98 (1H, m), 7.79 (1H, d, J 2.0 Hz), 4.60 (2H, s) and 2.71 (3H, s).
tart-Butyl7-bromomethylindole-1-carboxylate NMR 8H (400 MHz, CDCl3) 7.57 (1H, d, J 4.0 Hz), 7.55 (1H, dd, J 8.0, 1.5 Hz), 7.27 (1H, d, J 7.5 Hz), 7.19 (1H, t, J 7.5 Hz), 6.58 (1H, d, J 3.5 Hz), 5.24 (2H, s) and 1.68 (9H, s).
tent-Butyl 5-bromomethylindole-1-carboxylate NMR 8H (400 MHz, CDCl3) 8.11 (1H, br d, J 8.5 Hz), 6.72 (1H, d, J 3.5 Hz), 7.59 (1H, d, J
1.5 Hz), 7.35 (1H, dd, J 8.5, 1.5 Hz), 6.54 (1H, d, J 4.0 Hz), 4.64 (2H, s) and 1.67 (9H, s).
tent-Butyl 7-bromomethyl-5-chloroindole-1-carboxylate NMR ~H (400 MHz, CDCl3) 7.58 (1H, d, J 3.5 Hz), 7.51 (1H, d, J 2.0 Hz), 7.27 (1H, m), 6.52 (1H, d, J 3.5 Hz), 5.15 (2H, s), and 1.67 (9H, s).
tart-Butyl 7-bromomethyl-5-methylindole-1-carboxylate NMR 8H (400 MHz, CDC13) 7.53 (1H, d, J 4.0 Hz), 7.32 (1H, s), 7.09 (1H, s), 6.49 (1H, d, J 3.5 Hz), 5.21 (2H, s), 2.41 (3H, s) and 1.66 (9H, s).
tent-Butyl 5-bromomethyl-7-fluoroindole-1-carboxylate NMR bH (CDC13) 7.65 (1H, d, J 4.0 Hz), 7.35 (1H, d, J 1.5 Hz), 7.07 (1H, dd, J
13.0, 1.5 Hz), 6.56 (1H, dd, J 3.5, 1.5 Hz), 4.56 (2H, s) and 1.65 (9H, s).
tent-Butyl 5-bromomethyl-4-chloroindole-1-carboxylate NMR 8H (400 MHz, CDCl3) 8.03 (1H, d, J 8.5 Hz), 7.63 (1H, d, J 4.0 Hz), 7.36 (1H, d, 8.5 Hz), 6.71 (1H, d, J 3.5 Hz), 4.75 (2H, s) and 1.67 (9H, s).
tent-Butyl 7-bromo-5-bromomethylindole-1-carboxylate NMR 8H (400 MHz, CDC13) 7.57 (1H, s), 7.56 - 7.52 (2H, m), 6.54 (1H, d, J 3.5 Hz), 4.56 (2H, s) and 1.66 (9H, s).
tent-Butyl 5-bromomethyl-6-chloroindole-1-carboxylate NMR 8H (400 MHz, CDC13) 8.23 (1H, br s), 7.60 (1H, s), 7.58 (1H, d, J 3.5 Hz), 6.51 (1H, d, J 4.5 Hz), 4.71 (2H, s) and 1.67 (9H, s).
tent-ButylS-bromomethyl-6-fluoroindole-1-carboxylate NMR SH (400 MHz, CDC13) 7.88 (1H, br d, J 11.0 Hz), 7.57 (1H, d, J 4.0 Hz), ?.54 (1H, d, J 7.0 Hz), 6.52 (1H, d, J 4.5 Hz), 4.64 (2H, s) and 1.67 (9H, s).
tent-Butyl 2-bromomethyl-5-fluoroindole-1-carboxylate NMR 8H (400 MHz, CDCl3) 8.12 (1H, dd, J 9.0, 4.5 Hz), 7.15 (1H, dd, J 8.5, 2.5 Hz), 7.04 (1H, dt, J 9.0, 2.5 Hz), 6.66 (1H, s), 4.90 (2H, s) and 1.72 (9H, s).
tent-Butyl 5-bromomethyl-7-chloroindole-1-carboxylate NMR 8H (400 MHz, CDC13) 7.56 (1H, d, J 4.0 Hz), 7.49 (1H, d, J 2.0 Hz), 7.37 (1H, s), 6.54 (1H, d, J 3.5 Hz), 4.56 (2H, s) and 1.65 (9H, s).
2-(1-Bromopropyl)-5,6-dimethylpyridine 79 , NMR 8n (400 MHz, CDC13) 7.39 (1H, d, J 8.0 Hz), 7.18 (1H, d, J 8.0 Hz), 4.93 (1H, t, J
7.5 Hz), 2.49 (3H, s), 2.27 (3H, s), 2.29 - 2.24 (2H, m) and 1.02 (3H, t, J
7.0 Hz); M/Z 228 (M+H)''-.
The following novel compound was synthesised by bromination of 2-(1-methoxypropyl)-6-methylpyridine using Method AC.
2-Bromo-1-(6-methylpyridin-2-yl)propanone NMR 8H (400 MHz, CDCl3) 7.91 (SH, d, J 7.5 Hz), 7.74 (1H, t, J 7.5 Hz), 7.35 (1H, d, J
7.5 Hz), 6.13 (1H, q, J 7.0 Hz), 2.62 (3H, s) and 1.89 (3H, d, J 7.0 Hz).
Method AD
tart-Butyl 7-methylindole-1-carboxylate A stirred solution of 7-methylindole (1.18g, 9 mmol) in dry THF (50 mL) was treated with NaH (360 mg, 60 °lo in oil, 9 mmol), stirred for 10 min, treated with di-tart-butyl dicarbonate (2.3 mL, 9.3 mmol), stirred for 1 h, treated with 4-(N,N-dimethylamino)pyridine (catalytic amount) and stirred for 1 h. The mixture was partitioned between EtOAc (50 mL) and saturated NH4Cl solution (30 mL) and the organic phase was dried (MgS04), concentrated in vacuo, and purified by chromatography [Si02;
iso-hexane EtOAc (5:1)] to give the title compound (2.35 g, 100 %) as an orange oil; NMR
8n (400 MHz, CDC13) 7.51 (1H, d, J 4.0 Hz), 7.37 (1H, d, J 7.5 Hz), 7.13 (1H, t, J 7.5 Hz), 7.08 (1H, d, 7.5 Hz), 6.51 (1H, d, J 4.0 Hz), 2.64 (3H, s) and 1.63 (9H, s).
The following novel compounds were synthesised from the appropriate indoles using Method AD.
tart-Butyl 5-chloro-7-methylindole-1-carboxylate NMR 8H (400 MHz, CDCl3) 7.52 (1H, d, J 4.0 Hz), 7.35 (1H, d, J 2.0 Hz), 7.07 (1H, d, J
1.5 Hz), 6.46 (1H, d, J 3.5 Hz), 2.61 (3H, s), and 1.63 (9H, s).
tart-Butyl 5,7-dimethylindole-1-carboxylate NMR 8H (CDC13) 7.48 (1H, d, J 4.0 Hz) 7.16 (1H, s), 6.92 (1H, s), 6.44 (1H, d, J 4.0 Hz), 2.60 (3H, s) 2.38 (3H, s) and 1.62 (9H, s).
tent-Butyl 7-fluoro-5-methylindole-1-carboxylate 5 NMR SH (CDCl3) 7.59 (1H, d, J 4.0 Hz), 7.10 (1H, s), 6.84 (1Ha d, J 13.5 Hz), 6.50 - 6.47 (1H, m), 2.40 (3H, s) and 1.64 (9H, s).
tent-Butyl 4-chloro-5-methylindole-1-carboxylate NMR 8H (400 MHz, CDC13) 7.92 (1H, d, J 8.0 Hz), 7.57 (1H, d, J 3.5 Hz), 7.15 (1H, d, J
10 8.5 Hz), 6.66 (1H, d, J 3.5 Hz), 2.46 (3H, s) and 1.66 (9H, s).
tart-Butyl 7-bromo-5-methylindole-1-carboxylate NMR SH (400 MHz, CDCl3) 7.47 (1H, d, J 3.5 Hz), 7.35 (1H, s), 7.26 (1H, s), 6.44 (1H, d, J4.0 Hz), 2.38 (3H, s) and 1.64 (9H, s).
tent-Butyl 6-chloro-5-rnethylindole-1-carboxylate NMR 8H (400 MHz, CDCl3) 8.17 (1H, br s), 7.53 (1H, d, J 3.5 Hz), 7.38 (1H, s), 6.46 (1H, d, J 3.0 Hz), 2.44 (3H, s), 1.67 (9H, s).
tent-Butyl6-fluoro-5-methylindole-1-carboxylate NMR 8H (400 MHz, CDC13) 7.79 (1H, br d, J 10.5 Hz), 7.51 (1H, d, J 3.5 Hz), 7.30 (1H, d, J 7.5 Hz), 6.46 (1H, d, J 3.5 Hz), 2.34 (3H, s) and 1.66 (9H, s).
tent-Butyl 5-fluoro-2-methylindole-1-carboxylate NMR 8H (400 MHz, CDC13) 8.04 (1H, dd, J 9.0, 4.5 Hz), 7.07 (1H, dd J 9.0, 2.5 Hz), 6.92 (1H, dt, J 9.5, 3.0 Hz), 6.27 (1H, s), 2.58 (3H, d, J 1.5 Hz) and 1.67 (9H, s).
tent-Butyl 7-chloro-5-methylindole-1-carboxylate NMR bH (400 MHz, CDC13) 7.50 (1H, d, J 3.5 Hz), 7.22 (1H, s), 7.14 (1H, s), 6.46 (1H, d, J 4.0 Hz), 2.38 (3H, s) and 1.64 (9H, s).
The following novel compound was synthesised from 2,6-difluoro-4-hydroxybenzyl alcohol using Method AD.

tart-Butyl (3,5-difluoro-4-hydroxymethylphenyl) carbonate IR v~ (DR)/crri 1 3388, 2983, 1775, 1605, 1446, 1396, 1373, 1289, 1146, 1072, 967 and 882; NMR 8H (400 MHz, CDC13) 6.79 (2H, m), 4.75 (2H, d, J 6.5 Hz), 1.84 (1H, t, J 6.5 Hz) and 1.56 (9H, s).
Method AE
2,6-Difluoro-4-hydroxybenzyl alcohol A mixture of 3,5-difluorophenol (25 g, 0.19 mol) and KOH (85 %., 12.7 g, 0.19 mol) was treated dropwise with water (50 mL), stirred at 60 °C for 1 h, treated dropwise with formaldehyde solution (37 %, 15.6 mL, 0.19 mol) and water (50 mL) and stirred overnight at 40 °C. The mixture was cooled, acidified with 6-M HCl, filtered and the resulting solid washed with water and dried to give the title compound (15 g, 49 %) as a white solid:
NMR 8H (400 MHz, DMSO) 10.28 (1H, s), 6.43 (2H, m), 4.99 (1H, t, J 5.6 Hz) and 4.37 (2H, d, J 5.6 Hz).
Method AF
7-(2-Furyl)-3-(6-indolylmethyl)-3H-[1,2,3]triazolo(4,5-d]pyrimidine-5-amine (Example 152) A mixture of tart-butyl 6-(5-amino-7-(2-furyl)-3H [1,2,3]triazolo(4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate (135 mg, 4.08 mmol), and NaOMe (22 mg, 4.08 mmol) in MeOH (10 mL) was refluxed for 1 h, treated with NaOMe (110 mg, 20.4 mmol), refluxed for a further 4 h then stirred at room temperature for 17 h. The mixture was concentrated in vacuo to half volume and the resulting precipitate was filtered and washed with HZO to give the title compound (90 mg, 96 %) as a cream solid.
Method AG
3-(2,6-Difluoro-4-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 156) A solution of 3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride (130 mg, 0.34 mmol) in DMF (5 mL) at 0 °C, was treated with CsC03 (223 mg, 0.68 mmol), stirred for 10 min, treated with methyl iodide (21 p,L, 0.34 mmol) and stirred at room temperature for 30 min. The reaction mixture was diluted with water (10 mL) and filtered to give the title compound (122 mg, 100 %) as a white solid.
Method AH
2-Fluoro-5-iodobenzyl alcohol A solution of 2-fluoro-5-iodobenzaldehyde (1.173 g, 4.692 mmol) in isopropanol (25 mL) was treated with sodium borohydride (0.379 g, 10.02 mmol), stirred at room temperature for 18 h, poured into water. (125 mL), and extracted with isopropyl ether (2 x 25 mL). The combined organic phase was dried (Na2S04), and concentrated in vacuo to give the title compound (1.187 g, 99 %) as a pale yellow solid; NMR 8H (400 MHz, CDC13) 7.77 (1H, m), 7.57 (1H, m), 6.82 (1H, t, J 8.8 Hz), 4.73 (2H, d, J 6.1 Hz), and 1.79 (1H, t, J 6.1 Hz).
Method AI
3-(tent-Butoxycarbonyloxy)-4-nitrobenzoic acid A solution of 3-hydroxy-4-nitrobenzoic acid (1.83 g, 10 mmol) in THF (10 mL) was treated with Et3N (3.4 mL, 24 mmol) and di-tart-butyl dicarbonate (2.40 mL, 11 mmol) and stirred at room temperature for 16 h. The reaction mixture was poured into 10% citric acid solution (20 mL), extracted with EtOAc (2 x 10 mL), dried (MgS04) and concentrated irz vacuo to give the title compound (2.36 g, 83 %) as a cream solid; 1R v,~aX
(Nujol)/crri 1 2985, 1772, 1717 and 1592; NMR ~H (400 MHz, DMSO) 13.85 (1H, s), 8.26 (1H, d, J 8.5 Hz), 8.04 (1H, dd, J 8.5, 2.0 Hz), 7.98 (1H, d, J 2.0 Hz) and 1.49 (9H, s).
Method AJ
tent-Butyl (5-bromomethyl-2-nitrophenyl) carbonate A solution of 3-(tart-butoxycarbonyloxy)-4-nitrobenzoic acid (2.26 g, 8 mmol) and N-methylmorpholine (1.85 mL, 16.8 mmol) in THF (20 mL) at 0 °C, was treated with isobutylchloroformate (1.09 mL, 8.4 mmol) and stirred for 1 h. The reaction mixture was added to a cooled (-78 °C) solution of NaBH4 (605 mg, 16 mmol) in MeOH
(16 mL) and stirred at room temperature for 1 h. The reaction mixture was diluted with EtOAc (20 mL), washed with saturated NaHCO3 (10 mL) and 10% citric acid solution (10 mL), dried (MgS04) and concentrated itZ vacuo to give tent-butyl (5-hydroxymethyl-2-nitrophenyl) carbonate (1.36 g, 86 %) as a cream solid. This material was brominated directly using Method AB to give the title compound (961 mg, 58 %) as a yellow oil: NMR SH
(400 MHz, CDC13) 8.09 (1H, d, J 8.4 Hz), 7.41 (1H, dd, J 8.4, 2.0 Hz), 7.34 (1H, d, J 2.0 Hz), 4.47 (2H, s) and 1.58 (9H, s).
Method AK
3-(3-Nitrobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride (Example 266) A soluition of 7-chloro-3-(3-nitrobenzyl)-3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine (306 mg, 1 mmol), 1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-ylboronic acid (2 minol), Pd(PPh3)4 (100 mg) and saturated NaHC03 (5 mT.) in THF (20 mL) was refluxed for 2 h, diluted with water (20 mL), extracted with EtOAc(2 x 20 mL), dried (MgS04), concentrated in vacuo and purified by chromatography [SiOa; CH2C12 : EtOAc (6:1)] to give 3-(3-nitrobenzyl)-7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (156 mg, 34 %) as a pale yellow syrup.
A solution of 3-(3-nitrobenzyl)-7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (156 mg, 0.34 mmol) in MeOH (2 mL) was treated with 4-M HCl in dioxane (4 mL) stirred at room temperature for 2 h, concentrated in vacuo, triturated with Et20 and filtered to give the title compound (110 mg, 97 %) as a yellow solid.
Method AL
3-(6-Acetamidomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 177) A suspension of 7-(2-furyl)-3-(6-phthalimidomethyl-2-pyridylmethyl)-3H
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (210 mg, 0.465 mmol) in EtOH (50 mL) was treated with ethylenediamine (62 ~l, 0.929 mmol), stirred for 3 h at 90 °C and the resulting clear solution, cooled to room temperature and concentrated in vacuo to give 3-(6-aminomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine.
A solution of this material in pyridine (10 mL) at 0 °C was tareated with acetyl chloride (109 ml, 1.53 mmol), stirred for 10 min, poured into water (70 mL), extracted with EtOAc (3 x 20 mL) and the combined organic phase was dried (MgS04), concentrated in vacuo and purified by chromatography [Si02; EtOAc] to give the title compound (110 mg, 65 %) as a beige solid.
Method AM
3-(6-Allyloxymethyl-2-pyridylmethyl)- N,N-diallyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 182) A solution of 7-(2-furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (120 mg, 0.377 mmol) in DMF (5 mL) at 0 °C was treated with sodium hydride (30 mg, 0.743 mmol), stirred for 15 min, treated with allyl bromide (96 p1, 1.11 mmol), stirred at room temperature for 16 h, concentrated in vacuo to ~2 mL and purified by chromatography [SiOa; isohexane:EtOAc (3:1)] to give the title compound (50 mg, 30 %) as a yellow solid.
Method AN
6-Allyloxymethyl-2-pyridinemethanol A solution of 2,6-pyridinedimethanol (5.0 g, 35.9 mmol) in DMF (30 mL) at 0 °C was treated with sodium hydride (1.44 g, 35.9 mmol), stirred for 30 min, treated with allyl bromide (3.42 ml, 39.5 mmol), stirred for 16 h at room temperature, poured into water (150 mL), extracted with EtOAc (3 x 30 mL) and the combined organic phase was dried (MgS04), concentrated in vacuo and purified by chromatography [SiO2;
isohexane:EtOAc (3:1 to 1:1)] to give the title compound (1.56 g, 24 %) as a colourless oil:
NMR 8H (400 MHz, CDCl3) 7.69 (1H, t, J 7.5 Hz), 7.37 (1H, d, J 7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 6.04 -5.93 (1H, m), 5.38 - 5.21 (2H, m), 4.74 (2H, d, J 5.0 Hz), 4.65 (2H, s), 4.15 -4.09 (2H, m) and 3.76 (1H, t, J 5.0 Hz).
The following novel compounds were synthesised from the appropriate alcohols by Method AN
2-(1-Methoxypropyl)-6-methylpyridine NMR 8H (400 MHz, CDC13) 7.58 (1H, t, J 8.0 Hz), 7.18 (1H, d, J 8.0 Hz), 7.04 (1H, d, J
8.0 Hz), 4.17 (1H, dd, J 5.5, 7.5 Hz), 3.30 (3H, s), 2.55 (3H, s), 1.84 - 1.69 (2H, m) and 0.93 (3H, t, J 7.5 Hz).

6-Isobutyloxymethylpyridine-2-methanol NMR 8n (400 MHz, CDCl3) 7.69 (1H, t, J 7.5 Hz), 7.37 (1H, d, J 7.5 Hz), 7.13 (1H, d, J
7.5 Hz), 4.74 (2H, s), 4.63 (2H, s), 3.94 (1H, br s), 3.33 (2H, d, J 6.5 Hz), 1.91 - 2.01 (1H, m) and 0.96 (6H, d, J 6.5 Hz).

6-Isopropyloxymethylpyridine-2-methanol NMR ~H (400 MHz, CDCl3) 7.70 - 7.66 (1H, m), 7.39 (1H, d, J 7.5 Hz), 7.11 (1H, d, J 8.0 Hz), 4.74 (2H, s), 4.64 (2H, s), 3.75 (1H, sept, J 6.0 Hz) and 1.25 (6H, d, T
6.0 Hz).
10 Method AO
3-Isopropyl-4-nitrobenzyl bromide A solution of 4-nitrobenzyl bromide (432 mg, 2 mmol) in THF (5 mL) at -70 °C, was treated dropwise with isopropylmagnesium chloride (1 mL, 2-M in EtaO, 2 mmol), stirred for 1 h, treated with DDQ (499 mg, 2.2 mmol) and stirred at room temperature for 16 h.
15 The reaction mixture was poured into water (10 mL), extracted with EtOAc (2 x 10 mL), dried (MgS04), concentrated in vacuo and filtered. The resulting solid was purified by chromatography [Si02; EtOAc : Heptane (1:4)] to give the title compound (183 mg, 35 %) as a pale yellow solid which was used in the next reaction without further purification.
20 The following novel compound was also synthesised from 4-nitrobenzyl bromide using Method AO
3-Ethyl-4-nitrobenzyl bromide NMR 8H (400 MHz, CDCl3) 7.87 (1H, d, J 8.3 Hz), 7.37 (1H, s), 7.35 (1H, d, J
8.3 Hz), 25 4.47 (2H, s), 2.92 (2H, q, J 7.5 Hz) and 1.30 (3H, t, J 7.5 Hz).
Method AP
2-(Trimethylsilyl)ethoxymethyl 4-nitro-2-((2-trimethylsilyl)ethoxymethoxy)benzoic acid 30 A solution of 2-hydroxy-4-nitrobenzoic acid (1.83 g, 10 mmol) in THF (20 mL), was treated with N,N-diisopropylethylamine (3.92 mL, 22 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (3.46 mL, 20 mmol) and stirred for 16 h then purified directly by chromatography [Si02: EtOAc : heptane (1:4)] to give the title compound (5.82 mg, quantitative) as white solid which was used in the next reaction without further purification; NMR 8H (400 MHz, CDCl3) 8.09 - 8.07 (1H, m), 7.87 - 7.85 (2H, m), 5.50 (2H, s), 5.35 (2H, s), 3.78 (4H, t, J 8.5 Hz), 1.00 - 0.88 (4H, m), 0.00 (9H, s) and 0.03 (9H, s).
Method AQ
2-(2-Trimethylsilyl)ethoxymethoxy-4-nitrobenzyl alcohol A ~ ~ solution of 2-(trimethylsilyl)ethoxymethyl 4-nitro-2-(2 (trimethylsilyl)ethoxymethoxy)benzoic acid (2.91 mg, 5 mmol) in Et20 (10 mL) at 0 °C, was treated with LiAlH4 (190 mg, 22 mmol) and stirred for 30 min. The reaction mixture was poured into water (20 mL), extracted with EtOAc (2 x 10 mL), dried (MgS04) and concentrated in vacuo to give the title compound (L35 g, 91 %) as a slightly impure colourless oil; NMR 8H (400 MHz, CDCl3) 7.96 - 7.99 (1H, m), 7.90 (1H, dd, J
8.5, 2.0 Hz), 7.55 (1H, d, J 8.5 Hz), 5.35 (2H, s), 4.78 (2H, s), 3.80 - 3.74 (2H, m), '0.99 - 0.94 (2H, m) and 0.00 (9H, s).
Method AR
4,6-Diisopropyl-2-pyridinemethanol A solution of 2-pyridinemethanol (5.00 g, 45.8 mmol), conc. sulfuric acid (2.44 ml, 45.8 mmol), iron(II) sulfate heptahydrate (1.53 g, 5.50 mmol) and isopropyl iodide (13.7 ml, 137 mmol) in DMSO (150 mL) was treated dropwise with hydrogen peroxide (27.5wt% in H20, 17.0 mL, 137 mmol), with ice-bath cooling to maintain the internal temperature at 25-30 °C. A further portion of iron(II) sulfate heptahydrate (1.53 g, 5.50 mmol) was added, the mixture was allowed to cool to room temperature over 1 h, poured into water (500 mL), basified to pH 9 with 5-M NaOH, extracted with dichloromethane (3 x 100 mL) and the combined organic phase was dried (MgS04), concentrated i~. vacuo and purified by chromatography [SiO~; isohexane:EtOAc (3:2)] to give 4,6-diisopropyl-2-pyridinemethanol (500 mg, 6 %) as a colourless oil; NMR 8H (400 MHz, CDC13) 6.90 (1H, s), 6.85 (1H, s), 4.69 (2H, br s), 4.35 (1H, br s), 3.03 (1H, sept, J 7.0 Hz), 2.87 (1H, sept, J
7.0 Hz), 1.30 (6H, d, J 7.0 Hz) and 1.25 (6H, d, J 7.0 Hz), and 6-isopropyl-2-pyridinemethanol (900 mg, 13 %) as a colourless oil.

The following novel compound was also synthesised from 2-pyridinernethanol by Method AR.
6-n-Propyl-2-pyridinemethanol NMR SH (400 MHz, CDC13) 7.58 (1H, t, J 7.5 Hz), 7.03 (2H, t, J 7.5 Hz), 4.72 (2H, s), 4.15 (1H, br s), 2.77 (2H, t, J 7.5 Hz), 1.77 (2H, sept, J 7.5 Hz) and 0.97 (3H, t, J 7.5 Hz).
Method AS
tent-Butyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-carboxylate (Example 203) A solution of 7-(2-furyl)-1H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine (300 mg, 1.49 mmol) in DMF (5 mL), at 0 °C, was treated with 60% sodium hydride in mineral oil (60 mg, 1.49 mmol), stirred for 30 minutes, treated with tent-butyl 4-(bromomethyl)phenylcarbonate (471 mg, 1.64 mmol), stirred at room temperature for 16 h, and purified by chromatography [Si02; EtOAc: heptane, (1:2)] to give the title compound (55 mg, 12 %) as a beige solid.
Method AT
2-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylethanone (Example 211) A solution of 7-(2-furyl)-1H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine (101 mg, 0.5 mmol) in DMF (2 mL) was treated with 2-bromoacetophenone (100 mg, 0.5 mmol) and triethylamine (105 p,L, 0.75 mmol), stirred at room temperature for 3 days, diluted with water (100 mL) and filtered. The resulting solid was purified by chromatography [Si02;
Hexane: EtOAc, (3:1 to 1:1)] to give the title compound (20 mg, 13 %) as a yellow solid.
Method AU
7-(2-Furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride (Example 213) A solution of 6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)pyridine-2-carboxaldehyde (62 mg, 0.193 mmol) in MeOH (20 mL) was treated with acetic acid (5 mL), dimethylamine (2-M in MeOH, 1.93 mL, 3.86 mmol) and sodium cyanoborohydride (242 mg, 3.86 rnmol), stirred for 16 h and concentrated in vacuo. The residue was treated with saturated NaHC03 solution (20 mL), extracted with EtOAc (3 x mL) and the combined organic phase dried (MgS04), concentrated in vacuo and purified by chromatography [Si02; EtOAc] to give the free base as a yellow solid. The solid was suspended in MeOH (1 mL), treated with HCl (4-M in dioxane, 0.25 mL), stirred 5 for 10 min, concentrated in vacuo and triturated with EtaO to give the title compound (22 mg, 29 %) as a yellow solid.
Method AV
3-(6-Cyanomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-10 5-amine (Example 220) A solution of 3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H
[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (200 mg, 0.517 mmol) and sodium cyanide (51 mg, 1.03 mmol) in DMF (5 mL) was stirred at 60 °C for 16 h, poured into water (40 mL), extracted with EtOAc (3 x 8 mL), the combined organic phase dried (MgS04), concentrated in vacuo and purified by chromatography [SiO~;isohexane:EtOAc (1:1)] to give title compound (50 mg, 26 %) as a yellow solid.
Method AW
3-(4-Hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 221) A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (400 mg, 1.98 mmol) in DMF (3 mL), at 0 °C, was treated with 60% sodium hydride in mineral oil (80 mg, 1.98 mmol), stirred for 30 min, treated with 4-(2-(trimethylsilyl)ethoxymethoxy)benzyl bromide (1.23 g, 3.96 mmol}, stirred at room temperature for 48 h and purified by chromatography [Si02; EtOAc: heptane, (1:2)]. The resulting yellow solid was dissolved in MeOH:DMF (1:2), passed through an ion exchange cartridge (Isolute SPE SCX-2), concentrated in vacuo, and washed with water and ether to give the title compound (41 mg, 7 %) as a pale yellow solid.
Method AX
N-(3-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)propanesulphonamide (Example 224) A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrirnidine-5-amine (153 mg, 0.5 mmol) in pyridine (2 mL) at 0 °C was treated with propanesulfonyl chloride (62 p,L, 0.55 mmol) and shaken at room temperature for 16 h. The mixture was poured into water (50 mL), extracted with EtOAc (2 x 10 mL), washed with 10 % citric acid (10 mL) and the combined organic phase dried (MgS04) and concentrated in vacuo to give the title compound (111 mg, 54 %) as a cream solid.
Method AY
7-(2-Furyl)-3-(6-(N-methylamino)methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo [4,5-d]pyrimidine-5-amine (Example 226) A solution of N-methyl-2,2,2-trifluoroacetamide (197 mg, 1.55 mmol) in DMF (5 mL) at 0 °C was treated with sodium hydride (60 % dispersion in mineral oil; 62 mg, 1.55 mmol), stirred for 15 min, treated with 3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (120 mg, 0.310 mmol), stirred at 50 °C for 1 h, cooled to room temperature, poured into water (20 mL), extracted with EtOAc (3 x 10 mL) and the combined organic phase dried (MgS04) and concentrated in vacuo to give N-(6-(5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)-N-methyltrifluoroacetamide. A solution of this product in MeOH (20 mL) was treated with a solution of sodium (71 mg, 3.10 mmol) in MeOH (10 mL), stirred for 16 h, concentrated in vacuo, treated with EtOAc (20 mL), filtered through Celite and concentrated in vacuo. The resulting solid was suspended in MeOH (2 mL), treated with HCl (4-M in dioxane, 1.0 mL), stirred for 10 min, concentrated in vacuo and triturated with EtaO to give the title compound (80 mg, 58 %) as a yellow solid.
Method AZ
3-(1H-Benzotriazol-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-amine (Example 158) A mixture of 5-methyl-1H benzotriazole (666 mg, 5 mmol) in THF (20 mL) was treated with NaH (60 % dispersion, 200 mg, 5 mmol), stirred at room temperature for 10 min, treated with di-tart-butyl dicarbonate (115 mg, 5 mmol) and stirred overnight.
The mixture was treated with saturated NaHC03 solution (10 mL), extracted with EtOAc (2 x 10 mL), dried (MgS04), filtered through a plug of Si02 and concentrated in vacuo to give tart-butyl 5-methylbenzotriazole-1-carboxylate (as a, mixture with the 6-methyl regioisomer) (1.08 g, 92 %) as a colourless oil.
A solution of tent-butyl 5-methyl-1H-benzotriazole-1-carboxylate (as a mixture with the 6 methyl regioisomer) (1.08 g, 4.63 mmol), benzoyl peroxide (112 mg, 0.46 mmol) and N
5 bromosuccinnimide (0.76 g, 4.63 mmol) in CCl4 (25 mL) was refluxed overnight, cooled, filtered, concentrated in vacuo and purified by chromatography [Si02;
isohexane : EtOAc (10:1)] to give tent-butyl 5-(bromomethyl)-1H benzotriazole-1-carboxylate (666 mg, 46 %) (as a mixture with the 6-bromomethyl regioisomer) as a colourless oil.
A solution of 7-(2-furyl)-1H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine (404 mg, 2 mmol) 10 in DMF (4 mL) was treated with NaH (60 % dispersion, 80 mg, 2 mmol), stirred at room temperature for 10 min, treated with a solution of tart-butyl 5-(bromomethyl)-benzotriazole-1-carboxylate (as a mixture with the 6-bromomethyl regioisomer) (624 mg, 2 mmol) in DMF (2 mL) and stirred overnight. The mixture was concentrated in vacuo and purified by chromatography [SiOa, isohexane : EtOAc (2:1)] to give tart-butyl 5-(5-amino-15 7-(2-furyl)-3H-triazolo[4,5-d]pyrimidin-3-yl)methyl-1H benzotriazol-1-carboxylate (135 mg, 24 %) (as a mixture with the 6-substituted regioisomer) as a white solid.
A solution of tart-butyl 5-(5-amino-7-(2-furyl)-3H triazolo[4,5-d]pyrimidin-3-yl)methyl-1H-benzotriazol-1-carboxylate (as a mixture with.the 6-substituted regioisomer) (135 mg, 0.31 mmol) in MeOH (5 mL) and THF (5 mL) was treated with 40 % aqueous 20 dimethylamine (0.176 mL, 1.56 mmol), refluxed for 25 rnin, concentrated in vacuo and the resulting solid triturated with ether, filtered, triturated with MeOH, filtered and dried to give the title c~mpound (31 mg, 30 %) as a yellow solid.
Method BA
25 Ethyl 4-((5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl)methyl)-2-methylphenylcarbamate (Example 274) A suspension of 3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H [1,2,3]triazolo[4,5-d]pyrimidine-5-amine (260 mg, 0.812 mmol) in pyridine (5 mL) at room temperature was treated dropwise with ethyl chloroformate (0.155 mL, 1.62 mmol), stirred for 30 min, 30 poured into water (30 mL), extracted with EtOAc (2 x 10 mL) and the combined organic phase was dried (MgSO~) and concentrated in vacuo to give the title compound (318 mg, 100 %) as a beige solid.

Method BB
N-(4-(5-Amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-methylphenyl)formamide (Example 244) A mixture of ethyl 4-((5-amino-7-(2-furyl)-3H [1,2,3]triazolo[4,5-d]pyrimidine-yl)methyl)-2-methylphenylcarbamate (318 mg, 0.81 mmol) and LiAIH~ (62 mg, 1.62 mmol) in dry THF (30 mL) was refluxed overnight, cooled to room temperature, treated with 13 % aqueous NaOH solution (0.1 mL) then water (0.3 mL), stirred for 30 min, filtered through Celite and concentrated in vacuo. The resulting solid was triturated with THF and filtered to give the title compou~zd (20 mg, 7 %) as a yellow solid.
Method BC
7-Fluoro-5-methylindole A solution of chloral hydrate (7.3 g, 44 mmol), sodium sulphate decahydrate (52 g, 160 mmol) and HZO (100 mL) was added slowly to a stirred solution of 2-fluoro-4-methylaniline (5.0g, 40 mmol), hydroxylamine hydrochloride (11.1 g, 160 mrriol) and conc. HCl (3 mL) in H20 (50 mL). The reaction mixture was refluxed for 1 h, stirred at room temperature for 5 h, filtered and the resulting solid crystallised from MeOH / HBO to yield brown crystals (1.53 g). This material was added in small portions with stirring to cons. sulphuric acid (20 mL) at 70 °C, stirred for 1 h, then added slowly with rapid stirring to ice / H20 (200 mL), extracted twice with EtOAc (2 x 25 mL) and the combined organic phase dried (MgSO4) and concentrated in vacuo to give 7-fluoro-5-methylisatin (1.68 g, 24 %) as a dark red gum.
A solution of 7-fluoro-5-methylisatin (1.68 g, 9.43 mmol) in dry THF (50 mL) was added slowly to an ice cold, stirred suspension of LiAlH4 (1.18 g, 31 mmol) in dry THF (50 mL), ~ refluxed for 2 h, cooled to room temperature then treated sequentially with H20 (1.2 mL), 15 % NaOH (1.2 mL) and H20 (3 mL). The solution was filtered through a pad of Celite, washing the filter cake thoroughly with THF, the deep blue filtrate was concentrated in vacuo and purified by chromatography [Si02; iso-Hexane:EtOAc (9:1)] to give the title compound (480 mg, 41 %) as a pale blue oil; NMR 8H (CDCl3) 8.19 (1H, br s), 7.21 - 7.16 (2H, m), 6.74 (1H, d, J 12.0 Hz), 6.51 - 6.46 (1H, m) and 2.42 (3H, s).

Method BE
3-(7-Fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 246) A stirred suspension of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (303 mg, 1.5 mmol) in DMF (2 mL) was treated with NaH (60 % dispersion in oil, 60 mg, 1.5 mmol), stirred for 10 min, treated slowly with a solution of tent-butyl 5-bromomethyl-7 fluoroindole-1-carboxylate (460 mg, 1.5 mmol) in DMF (1 mL), stirred for 2 h then the mixture was purified directly by chromatography [Si02; iso-hexarie:EtOAc (2:1)] to give the BOC protected product (180 mg, 0.417 mmol) as a pale green solid. This material was dissolved in MeOH (5 mL), treated with sodium methoxide (113 mg, 2 mmol), refluxed for 4 h, cooled to room temperature, diluted with HZO and filtered to give the title compound (118 mg, 81 %) as a cream solid.
Method BF
3-(3-(4-Fluorobenzylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (Example 252) A suspension of 3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (200 mg, 0.65 mmol) and 4A molecular sieves in THF (10 mL) was treated with 4-fluorobenzaldehyde (0.04 mL, 0.37 mmol), heated to 40 ~C for 3 h, cooled to room temperature, treated sodium triacetoxyborohydride (400 mg, 1.89 mmol) and acetic acid (0.1 mL) and stirred for 15 minutes. The reaction was quenched by addition of sat.
NaHCO3 (5 mL), extracted with EtOAc (2 x 5 mL) and the combined organic phase dried (MgSO4), concentrated in vacuo and purified by chromatography [(Si02; EtOAc :
Heptane (1:2)] to give the title compound (60 mg, 44 %) as a white solid..
Method BG
2-(2-Methoxyethyl)-6-(triphenylmethoxy)methylpyridine A stirred solution of (methoxymethyl)triphenylphosphonium chloride (2.79 g, 8.13 mmol) in THF (50 mL) at 0 °C was treated dropwise with n-BuLi (1.6-M in hexanes, 5.08 mL, 8.13 mmol), stirred for 1 h, treated with a solution of 6-(triphenylmethoxy)methylpyridine-2-carboxaldehyde (1.54 g, 4.06 mmol) in THF (15 mL) and allowed to warm to room temperature overnight. The reaction was treated with saturated NHa.CI solution (5 mL), diluted with water (50 mL), extracted with EtOAc (2 x 50 mL) and the combined organic phase diluted with iso-hexane (50 mL), dried (MgS04), filtered through silica and concentrated in vacuo to give 2-(2-methoxyethenyl)-6-(triphenylmethoxy)methylpyridine (1.58 g) as a yellow oil. A solution of this crude alkene and 10% Pd/C (216 mg, 0.203 mmol) in EtOAc (50 mL) was stirred under a hydrogen atmosphere for 16 h, filtered through Celite and concentrated in vacuo to give the title compound (1.08 g, 65 %) as a yellow oil; NMR 8H (400 MHz, CDCl3) 7.67 - 7.64 (1H, m), 7.52 - 7.49 (6H, m), 7.32 -7.21 (10H, m), 7.09 - 7.07 (1H, m), 4.34 (2H, s), 3.69 (2H, t, J 6.5 Hz), 3.32 (3H, s) and 2.98 (2H, t, J 6.5 Hz); M/Z 410 (M+H)+.
Method BH
2-Bromomethyl-6-(2-methoxyethyl)pyridine A solution of 2-(2-methoxyethyl)-6-(triphenylmethoxy)methylpyridine (1.08 g, 2.64 mmol) in 4-M HCl in dioxan (10 mL, 40.0 mmol) was stirred for 4 h and concentrated in vacuo. The residue was partitioned between dichloromethane (15 mL) and saturated NaHCO3 solution (15 mL), the aqueous phase was extracted with dichloromethane (10 mL) and the combined organic phase was dried (MgS04) and concentrated in vacuo to give 6-(2-methoxyethyl)pyridine-2-methanol. A solution of this product in dichloromethane (40 mL) at 0 °C was treated with triphenylphosphine (830 mg, 3.16 mmol) followed portionwise by carbon tetrabromide (1.31 g, 3.96 mmol), stirred for 1 h, concentrated i~c vacuo and purified by chromatography [SiO2; isohexane:EtOAc (4:1)] to give the title compound (303 mg, 50 %) as a yellow oil; NMR ~H (400 MHz, CDC13) 7.60 (1H, t, J 7.5 Hz), 7.28 (1H, d, J 7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 4.53 (2H, s), 3.76 (2H, t, J 6.5 Hz), 3.35 (3H, s) and 3.05 (2H, t, J 6.5 Hz).
Experimental data for Examples 1- 274 are provided in Table 2.
HPLC is carried out using the following conditions: Column. Waters Xterra RP
18 (50 x 4.6 mm); Particle size 5 p,M; Mobile phase MeOH : 10 mM aq NH4.OAc (pH 7 buffer);
Gradient 50:50 isocratic for 1 min. then linear gradient 50:50 to 80:20 over 5 min. then 80:20 isocratic for 3 min.; Flow rate 2.0 mL/min.; Detection wavelength ~, =
230 nM.
Retention times are provided in Table 2.

Table 2 o b% Physical Data b W ~

IR v",aX (Nujol)/czri 13403, 3329, 3134, 2925, 1656, 1634, 1582, 1565, 1463 and 1377;

NMR 8H (400 MHz, DMSO) 6.83 - 6.87 (1H, m), 7.12 (2H, s), 7.89 (1H, d, J 3.1 Hz), 8.09- 8.10 (1H, m), 15.52 (1H, s); M/Z 203 (M+H)+.

IR v~X (Nujol)/cni' 2924, 2854, 1612, 1587, 1526, 1489, 1456, 1372, 1221 and 753; NMR SH (400 MHz, DMSO) 4.98 (2H, s), 5.14 (2H, s), 5.71 (2H, s), 6.85 -2 B 11 6.87 ( 1H, m), 7.00 - 7.14 (3H, m), 7.14 - 7.46 (9H, m), 7.89 (1H, d, J 3.5 Hz), 8.16 (1H, d< J 1.0 Hz); Anal. Calcd for Cz9HziF3N6O
~ 0.25 HZO: C, 65.59; H, 4.08; N, 15.83. Found: C, 65.46; H, 4.03; N, 15.76.

IR v",aX (Nujol)/crri 13480, 3312, 3195, 3118, 2925, 2854, 1652, 1609, 1581, 1487, 1456, 1436, 1027 and 759; NMR 8H (400 MHz, DMSO) 5.60 (2H, s), 6.84 - 6.86 (1H, m), 7.15 - 7.29 (3H, m), 7.32 - 7.43 (3H, m), 7.89 (1H, d, J 2.9 Hz), 8.12 (1H, s).

mp 221.0 - 221.1 C; IR v",aX (Nujol)/cni l 3470, 3310, 3191, 3144, 2924, 2854, 1642, 1610, 1521, 1463 and 1354; NMR 8H (400 MHz, DMSO) 5.85 (2H, s), 4 B 9 6.87 (1H, s), 7.37 (2H, s), 7.63 - 7.73 (2H, m), 7.91 (1H, d, J 2.8 Hz), 8.13 (1H, s), 8.18 (1H, s), 8.20 (1H, s). Anal. Calcd for C15H1zN~03:
C, 50.57; H, 3.11; N, 27.52. Found: C, 50.99; H, 3.23; N, 27.21.

mp 259.8 - 259.9 C; IR v",aX (Nujol)/crxi' 3452, 3367, 3318, 3185, 3142, 2922, 1651, 1602, 1514, 1463 and 1377; NMR 8H (400 MHz, DMSO) 5.09 (2H, s), 5.49 (2H, s), 6.35 (1H, s), 6.41 (1H, d, J7.5 Hz), C 92 6.45 (1H, d, J 8.0 Hz), 6.85 -6.86 (1H, m), 6.96 (1H, t, J 8.0 Hz), 7.30 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.11 (1H, s). Anal. Calcd for C15Hi3N~0: C, 56.63; H, 4.50; N, 30.82. Found: C, 56.82; H, 4.25; N, 30.57.

1R v~X (Nujol)/cna' 3405, 3328, 3211, 3155, 2925, 2854, 1719, 1603, 1577, 1463, 1023 and 731; NMR 8n (400 MHz, DMSO) 3.84 (3H, s), 5.76 (2H, s), 6.85 6 B 21 - 6.87 (1H, m), 7.33 - 7.38 (2H, s), 7.50 - 7.59 (2H, m), 7.89 - 7.92 (3H, s), 8.12 - 8.13 (1H, m); Anal. Calcd for Cl~H1aN603 ~ 0.25 HzO: C, 57.54; H, 4.12; N, 23.68. Found: C, 57.42; H, 3.75; N, 23.37.

IR v",aX (Nujol)/crri 13506, 3309, 3189, 3131, 2925, 2854, 1635, 1606, 1580, 1502, 1417, 1204, 1025 and 762; NMR 8H (400 MHz, DMSO) 3.70 (6H, s), 5.58 7 B 27 (2H, s), 6.44 (3H, s), 6.84 - 6.87 (1H, m), 7.34 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.11- 8.12 (1H, m); Anal. Calcd for C1~H216N6~3 ' 0.5 H20: C, 56.50; H, 4.74;

N, 23.26. Found: C, 56.44; H, 4.56; N, 22.98.

IR v",~X (Nujol)/crn 13488, 3314, 3146, 2922, 2853, 1667, 1608, 1583, 1463 and 1378; NMR 8H (400 MHz, DMSO) 5.79 (2H, s), 6.84 - 6.87 (1H, m), 7.01 (1H, d, J 4.0 Hz), 7.05 ( 1H, d, J 4.0 Hz), 7.38 (2H, s), 7.89 ( 1H, d, J 3.5 Hz), 8.11-8.13 (1H, m).

IR v~X (Nujol)/crri' 3458, 3299, 3174, 3111, 2923, 1625, 1605, 1463 and 1377;

NMR 8H (400 MHz, DMSO) 3.61 (3H, s), 5.58 (2H, s), 6.84 - 6.94 (3H, m), 7.06 9 D 14 - 7.11 (1H, d, J 8.5 Hz), 7.19 (1H, t, J 8.0 Hz), 7.34 (2H, s), 7.64 - 7.67 (2H, m), 7.91 (1H, d, J 3.0 Hz), 8.12 (1H, s), 10.21 (1H, s); Anal. Calcd for C29H21F3N6O

0.25 H2O: C, 65.59; H, 4.08; N, 15.83. Found: C, 65.46; H, 4.03; N, 15.76.

IR v~X (Nujol)/cni 1 3404, 3313, 3202, 3122, 2923, 2854, 1724, 1639, 1609, 1557, 1456, 1407 and 1379; NMR ~H (400 MHz, DMSO) 4.60 (2H, d, J 6.0 Hz), 6.86 - 6.89 (1H, m), 7.25 - 7.32 (1H, m), 7.33 -7.44 (4H, m), 7.67 (2H, s), 7.91 (1H, d, J 3.5 Hz), 8.14 - 8.16 (1H, m), 9.25 (1H, t, J 6.0 Hz).

IR v~X (Nujol)/cni 1 3327, 3207, 2924, 2854, 1650, 1602, 1583, 1566, 1513 and 1487; NMR 8H (400 MHz, DMSO) 3.72 (3H, s), 5..63 (2H, s), 6.80 (1H, d, J7.5 11 B 40 Hz), 6.85 - 6.89 (3H, m), 7.26 (1H, t, J7.5 Hz), 7.33 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.11 (1H, s); Anal. Calcd for CIgHI,~IVgO2 ~ 0.25 HZO: C, 58.80; H, 4.47; N, 25.71. Found: C, 58.90; H, 4.40; N, 25.75.

1R ymlX (Nujoll/cmi 13374, 3311. 3202, 1636, 1606 1586, 1530. 1511 1465 1439, 1377 and 1343: NMR 8u (400 MHz DMSO) 6.03 (2H s) 6 86 - 6 89 ( 1H

12 B 21 m), 6.98 (1H. d, J7.5 Hz). 7.36 (2H, s) 7.60 - 7.73 (2H m) 7.92 (1H d J 3.5 Hzh 8.14 (1H, s1 8.211H, d, J 8.0 HzO Anal. Calcd for C,SH1,N?Q ~ 0.35 H~O:

C. 52.43; H, 3.43; N. 28.54. Found: C, 52.51; H
3.33 N. 28.21.

IR yma,~(Nujol)/crri 1 3489, 3313, 3191 1638 1603 1505, 1460 and 1378 NMR

SH (400 MHz. DMSO) 5.27 (2H, s) 5.47 (2H s) 6.50 (1H, t J 7.5 Hz) 6.67 -6.78 (2H, m), 6.86 (1H, s), 7.01 (1H, t J 7.0 Hz) 7.36 (2HLs), 7.90 (1H d J 3.0 Hz), 8.12~1H, s).

1R v",ax (Nujol)/cmi 13447, 3327, 3205, 2922, 2853, 1725, 1652, 1611 and 1458;

NMR 8H (400 MHz, DMSO) 8.13 (1H, d, J 1.0 Hz), 7.90 (1H, d, J 3.5 Hz), 7.38 14 F 35 (2H, s), 6.87 - 6.85 (1H, m), 5.40 (2H, s), 4.18 (2H, q, J 7.0 Hz) and 1.21 (3H, t, J 7.0 Hz); Anal. Calcd for C1~H12N602+ 0.2 HzO: C, 49.38; H, 4.28, N, 28.79.

Found: C, 49.25; H, 4.09; N, 28.47.

IR v~X (Nujol)/cni 13490, 3307, 3189, 2230, 1959, 1728, 1642, 1611, 1583, 1565, 1463, 1377, 1283, 1234, 1030 and 761; NMR 8H
(400 MHz, DMSO) 5.75 (2H, s), 6.82 - 6.89 (1H, m), 7.35 (2H, s), 7.57 - 7.59 (2H, m), 7.79 - 7.81 (2H, m), 7.91 (1H, d, J 3.5Hz), 8.12 (1H, s).

IR v",aX (Nujol)/crri 13309, 3184, 2726, 1639, 1608, 1585, 1456, 1377, 1026, 1002, 953 and 750; NMR ~ (400 MHz, DMSO) 2.22 (2H, quin, J 7.OHz), 2.67 16 B 6 (2H, t, J 7.OHz), 4.45 (2H, t, J 7.OHz), 6.83 - 6.88 (1H, m), 7.23-7.35 (3H, m), 7.66 (1H, dt, J 8.0, 2.OHz), 7.89 (1H, dd, J 3.5, l.OHz), 8.10 - 8.13 (1H, m);

Anal. calcd for C16H1sN~0 ~ 0.6 H20: C, 57.86; H, 4.92; N, 29.52. Found: C, 57.58; H, 4.53; N, 29.66.

IR v,~X (Nujol)/cni 13379, 3336, 3208, 1655, 1604, 1513, 1456, 1325, 11687, 1124, 1025 and 755; NMR 8H (400 MHz, DMSO) 5.79 (2H, s), 6.83 - 6.88 (1H, 17 B 7 m), 7.36 (2H, s), 7.53 (1H, d, J 7.5 Hz), 7.60 (1H, t, J 7.5Hz), 7.67 - 7.76 (2H, m), 7.91 (1H, d, J 3.5Hz), 8.13 (1H, s); Anal. Calcd, for C16H11FsN60: C, 53.34;

H, 3.08; N, 23.31. Found: C, 53.38; H, 3.18; N, 23.15.

IR vt"aX (Nujol)/crri 13451, 3206, 2361, 2261, 1655, 1604, 1459, 1378, 1195, 18 G 1001028 and 774; NMR SH (400 MHz, DMSO) 5.57 (2H, s), 6.57 - 6.63 (1H, rn), 6.65 - 6.74 (2H, m), 6.83 - 6.88 (1H, m), 7.14 (1H, t, J 7.5 Hz), 7.91 (1H, d, J

3.0 Hz), 8.12 (1H, d, J 1.0 Hz).

mp 291.8 - 292.0 C; IR vI"aX (DR)/cm-1 3436, 3178, 1651, 1615, 1398, 1226, 19 J 77 1029 and 977; NMR 8n (400 MHz, DMSO) 15.5 - 15.3 (1H, br s), 7.84 (1H, d, J

3.5 Hz), 7.07 (2H, br s), 6.48 (1H, dd, J 3.5, J
1.0 Hz), 2.44 (3H, s).

mp 213.5. - 213.7 C; IR v~X (DR)/crri 1 3300, 3218, 3098, 2957, 2927, 2744, 2368, 1645, 1602, 1570, 1537, 1508, 1490, 1438, 1328 and 1233; NMR ~H (400 MHz, DMSO) 7.86 (1H, d, J 3.0 Hz), 7.43 - 736 (1H, m), 7.31 (2H, br s), 7.28 -7.15 (3H, m), 6.50 (1H, dd, J 1.0, J 3.5 Hz), 5.68 (2H, s) and 2.45 (3H, s).

~ v~" (DR)/cni 13151, 2360, 1654, 1182, 998, 824, 681, and 572; NMR 8H

21 I~ 99 (400 MHz, DMSO) 10.28 (1H, d, J 2.0 Hz) and 9.73 (1H, d, J 2.5 Hz) IR v~X (DR)/crri 13479, 3289, 3169, 1597, 1502, 1226, 1119, 999, 880 and 757;

22 A 8 NMR 8H (400 MHz, DMSO) 9.43 (1H, s), 9.25 (1H, s), 7.48 - 7.34 (3H, m) 7.30 - 7.22 (2H, m), 7.21 - 7.15 (1H, m) and 5.72 (2H, s).

mp 187.3 -187.7 C; 1R v~X (DR)/crri 13993, 3489, 3319, 3197, 2951, 2725, 2353, 1954, 1719, 1633, 1604, 1503, 1420, 1232, 1032 and 740 ; NMR SH (400 MHz, DMSO) 2.27 (3H, s) 5.62 (2H, s), 6.82 - 6.88 (1H, rn), 7.02 - 7.16 (3H, m), 7.24 (1H, t, J 7.5 Hz), 7.33 (2H, s), 7.90 (1H, d, J 3.5 Hz) 8.12 (1H, s).

mp 196.9 -197.1 C; IR v~x (DR)/crri 13448, 3321, 3200, 1649, 1616, 1509, 1488; NMR ~H (400 MHz, DMSO) 8.49 - 8.47 (1H, m), 8.12 - 8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.81 - 7.77 (1H, m), 7.34 - 7.30 (1H, m), 7.27 (2H, br s), 7.24 (1H, d, J 8.0 Hz), 6.86 - 6.85 (1H, m), 5.77 (2H,s).

IR v~X (DR)/cni 13326, 3211, 2956, 2856, 1641, 1612, 1507, 1491; NMR ~H

(400 MHz, CDCl3) 8.77 - 8.76 (1H, m), 8.58 - 8.56 (1H, m), 8.08 (1H, d, J 3.5 25 N 50 Hz), 7.78 (1H, m), 7.75 - 7.72 (1H, m), 7.29 - 7.25 (1H, m), 6.71 - 6.69 (1H, m), 5.68 (2H, s), 5.37 (2H, br s); Anal. Calcd for C1dH11N~0 ~ 0.2 H20 ~ 0.4 C~H80z:

C, 56.41; H, 4.43, N, 29.52. Found: C, 56.10; H, 4.33; N, 29.52.

mp 291.0 - 291.1 C; 1R v~X (Nujol)/crri 13401, 3317, 3205, 2995, 1714, 1646, 1615, 1587, 1483 and 1247; NMR 8H (400 MHz, DMSO) 13.58 -13.31 (1H, s), 26 O 85 8.12 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.36 (2H, s), 6.87 - 6.86 (1H, m) and 5.29 (2H, s); Anal. Calcd for CloH8N603 ~ 0.6 H20: C, 44.32; H, 3.42, N, 31.01.

Found: C, 44.26; H, 3.07; N, 30.74.

mp 209.9 - 210.1 C; IR v,i,aX (DR)/crri l 3504, 3312, 3201, 2948, 161 l, 1503, 1435, 1279, 1220, 1025 and 755; NMR 8H (400 MHz, DMSO) 5.69 (2H, s), 6.82 27 B 19 - 6.87 (1H, m), 7.19 - 7.25 (1H, m), 7.33 (2H, s), 7.37 - 7.40 (3H, m), 7.90 (1H, d, J 3.5 Hz), 8.10 - 8.13 (1H, m). Anal. Calcd for C15H11NeOC1 ~ 0.2 H20: C, 54.54; H, 3.48; N, 25.44. Found: C, 54.69; H, 3.33;
N, 25.09.

IR v",aX (DR)/crri 1 3282, 2852, 1630, 1368, 1120, 871and 618; NMR 8H (400 28 K 40 MHz, DMSO) 7.94 (1H, d, J 2.5 Hz), 7.45 - 7.36 (2H, m), 7.29 - 7.22 (2H, m), 7.21 - 7.16 (1H, m) and 5.71 (2H, s).

IR v",aX (DR)/cni 13999, 3483, 3438, 3310, 3207, 2950, 2732, 2452, 1846, 1657, 29 B 8 1486, 1312, 1030 and 754; NMR 8H (400 MHz, DMSO) 4.02 (3H, s), 6.81- 6.88 (1H, m), 7.25 (2H, s), 7.88 (1H, d, J 3.5 Hz), 8.09 - 8.11 (1H, m).

IR v~X (Nujol)/cni 13500 - 3200, 2946, 2835, 1700 and 1523; NMR 8H (400 30 P 39 MHz, DMSO) 8.11 (1H, s), 7.89 (1H, d, J3.5 Hz), 7.69 (1H, s), 7.34 (1H, s), 7.26 (2H, s), 6.87 - 6.84 (1H, m) and 5.08 (2H, s).

IR v~x (Nujol)/cni 13457, 3313, 1666, 1617, 1523 and 1442; NMR 8H (400 MHz, DMSO) 10.68 (1H, s), 8.12 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.75 (1H, s), 31 P 48 7.45 (1H, d, ,~ 8.0 Hz), 7.37 (1H, t, J 8.0 Hz), 7.30 (2H, s), 7.15 (1H, d, J 8.0 Hz), 6.88 - 6.84 (1H, m and 5.39 (2H, s); Anal. Calcd for C16H12N~OzC1 ~ 0.8 H20: C, 50.02; H, 3.57, N, 25.27. Found: C, 50.15; H, 3.48;
N, 25.12.

mp 191.4 -192.0 C; IR v,i,ax (DR)/cxri 13511, 3306, 3194, 2955, 1638, 1476;

NMR 8H (400 MHz, DMSO) 8.12 - 8.11 (1H, m), 7.91 (1H, dd, J 3.5, 1.0 Hz), 32 N 76 7.66 (1H, dd, J 8.0, 7.0 Hz), 7.27 (2H, br s), 6.87 - 6.85 (1H, m), 6.73 - 6.70 (2H, m), 5.69 (2H, s), 3.68 (3H, s); Anal. Calcd for C15H13N~Oz ~ 0.2 CaHgOz: C, 55.66; H, 4.32, N, 28.76. Found: C, 55.88; H, 4.17;
N, 28.59.

mp 204.1- 204.2 C;1R v~X (DR)lcrri 13490, 3321, 3200, 2923, 2711, 2490, 1749, 1605, 1502, 1376, 1272, 1034 and 761; NMR 8H
(400 MHz, DMSO) 5.83 33 B 11 (2H, s), 6.83 - 6.86 (1H, m), 7.01 (1H, dd, J 5.0, 3.5 Hz), 7.16 (1H, dd, J 3.5, 1.0 Hz),~7.34 (2H, s), 7.48 (1H, dd, J 5.0, 1.5 Hz), 7.89 (1H, d, J 3.5 Hz), 8.09 - 8.12 (1H, m).

mp 225 - 230 C; IR v",aX (DR)lcmi 13520, 3344, 1734, 1611, 1438, 1240, 996, 833 and 761; NMR SH (400 MHz, DMSO) 8.26 (1H, d, J 3.0 Hz),.8.15 (1H, d, J

3.0 Hz), 7.50 - 7.44 (2H, br s), 7.42 - 7.36 (1H, m), 7.29 - 7.21 (1H. m), 7.21 -7.15 (1H, m) and 5.73 (2H, s).

mp 174.0 - 174.2 C;1R v",aX (DR)/cxri 1 3473, 3317, 3188, 2740, 1736, 1648, 1243, 1004 and 752; NMR SH (400 MHz, DMSO) 8.68 (1H, dd, J 4.0, 1.5 Hz), 7.99 (1H, dd, J 5.0, 1.0 Hz), 7.43 - 7.35 (2H, m), 7.31 - 7.16 (5H, m) and 5.71 (2H, s).

mp 231.7 - 234.0 C; IR v~X (DR)/crri 13498, 3404, 3309, 2931, 1607, 1539, 1498, 1317, 1101 and 1027; NMR 8H (400 MHz, DMSO) 7.86 (1H, dd, J 0.5, 36 C 50 3.5Hz), 7.24 (2H, br s,), 6.96 (1H, t, J 7.8 Hz), 6.50 (1H, dd, J 1.0, 3.5Hz), 6.48 -6.43 (1H, m),6.43 - 6.38 (1H, m), 6:36 (1H, t, J
1.7 Hz), 5:46 (2H, s), 5.07 (2H, br s) and 2.43 (3H, s).

mp 2.00.8 - 218.9 C; NMR SH (400 MHz, DMSO) 8.12 - 8.11 (1H, m), 7.91 37 N 60 (1H, d, J 3:5 Hz), 7.64 (1H, t, J 7.5 Hz), 7.29 (2H, br s), 7.18 (1H, d, J 7.5 Hz), 6.90 (1H, d, J 7.5 Hz), 6.86 - 6.85 (1H, m), 5.70 (2H, s) and 2.42 (3H,s).

mp 242.0 - 242.1 C; IR v~X (DR)/crri 13513, 3294, 1570, 1234, 999 and 755;

38 Q 35 NMR 8x (400 MHz, DMSO) 7.96 (1H, s), 7.46 - 7.34 (3H, m), 7.30 - 7:13 (3H, m), 5.72 (2H, s) and 2.60 (3H, s).

IR v,~,aX (Nujol)/crri' 3464, 3340, 3189, 2966, 2748, 1692, 1643 and 1605; NMR

Sx (400 MHz, DMSO) 8.11- 8.09 (1H, m), 7.90 (1H, 39 B 26 d, J 3.5 Hz), 7.33 - 7.24 (4H, m), 7.19 - 7.12 (2H, m), 7.09 (1H, s), 6.86 - 6.84 (1H, m), 5.64 (2H, s), 4.07 (2H, d, J 6.O~Hz) and 1.33 (9H, s).

IR v~x (Nujol)/crri' 3474, 3323, 3184, 3006, 2971, 2941, 2837, 1648, 1606 and 1496; NMR 8x (400 MHz, DMSO) 8.13 - 8.10 (1H, m), 7.90 (1H, d, J 3.5 Hz), 7.32 (2H, s), 6.98 (1H, d, J 9.0 Hz), 6.89 - 6.84 (2H, m), 6.48 (1H, d, J 3.0 Hz), 5.57 (2H, s), 3.76 (3H, s) and 3.62 (3H, s).

mp 213.8 -213.9 C;1R v~X (DR)/crri 13996, 3654, 3507, 3320, 2930, 2562, 2621, 1944, 1837, 1676, 1428, 1230, 1095, 1026 and 797; NMR 8x (400 MHz, DMSO) 5.65 (2H, s), 6.81- 6.86 (1H, m), 7.16 (2H, 41 B 32 t, J 8.5 Hz), 7:31 (2H, s), 7.44 - 7.56 (1H, m), 7.86 (1H, dd, J 3.5, 1.0 Hz), 8.07 - 8.13 (1H, m). Anal.

Calcd for ClSH,oN6OFz: C, 54.88; H, 3.07; N, 25.59.
Found: C, 54.57; H, 3.05;

N, 25.23.

mp 265.7 - 26.2 C; IR v,~X (DR)/crri 13491, 3370, 3120, 1614, 1232, 972, 753 42 Q 29 and 514; NMR 8x (400 MHz, DMSO) 7.72 (1H, s), 7.51 - 7.43 (2H, s), 7.42 -7.35 (1H, m), 7.30 - 7.14 (3H, m), 5.73 (2H, s) and 2.55 (3H, s).

mp 281.1- 280.2 C;1R v,~X (DR)icrri' 3466, 3326, 1641, 1503, 1379, 1240, 1056, and 825; NMR ~x (400 MHz, DMSO) 15.5 (1H, 43 H 65 br s), 8.6 (1H, dd, J 1.0, 4.0 Hz), 7.96 (1H, dd, J 1.0, 5.0 Hz), 7.36 (1H, dd, J 4.0, 5.0 Hz) and 7.0 (2H, br s).

IR v,~X (DR)/cni' 3255, 1686, 1590, 1458; NMR Sx (400 MHz, DMSO) 11.24 44 S/T 28 (1H, s), 8.95 - 8.94 (1H, m), 8.37 - 8.35 (1H, m), 8.08 - 8.07 (1H, m), 7.96 - 7.95 (1H, m), 7.68 (1H, d, J 8.0 Hz), 6.85 - 6.84 (1H, m).

mp 190.4 - 190.8 C; IR v~X (DR)lcni 13322, 3162, 1665, 1576, 1351, 1119, 45 A 59 1000, 809 and 604; NMR Sx (400 MHz, DMSO) 9.44 (1H, s), 9.26 (1H, s), 8.24 - 8.16 (2H, m), 7.95 (1H, s), 7.74 = 7.63 (2H, m), 7.45 (2H, br s) and 5.87 (2H, s).

IR v~X (Nujol)/crri 12967, 1651 and 1463; NMR 8x (400 MHz, DMSO) 8.35 -8.24 (3H, s), 8.14 - 8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.47 - 7.39 (2H, m), 7.36 - 7.31 (2H, s), 6.88 - 6.84 (1H, m), 5.67 (2H, s) and 3.98 (2H, q, J 5.5 Hz);

Anal. Calcd for ClsHISN~O ~ 2HCl ~ 0.9 H20: C, 46.82;
H, 4.62, N, 23.89. Found:

C, 47.10; H, 4.40; N, 23.84.

IR v~X (Nujol)/crri 13375, 3194, 2929, 2753, 1732, 1657, 1515, 1400 and 1334;

NMR 8H (400 MHz, DMSO) 8.14 - 8.11 (1H, m), 7.90 (1H, d, J 3.0 Hz), 7.45 -47 B 26 7.29 (6H, m), 6.88 - 6.84 (1H, m), 5.71 (2H, s), 2.95 (3H, s) and 2.85 (3H, s);

Anal. Caled for Cl$H1~N~02 ~ 0.5 HZO: C, 58.06; H, 4.87, N, 26.33. Found: C, 58.16; H, 4.65; N, 26.06.

mp 265.9 - 266.0 C; IR v~X (DR)/cni 1 3448, 3363, 3316, 3189, 1645, 1597, 1511, 1440 and 1103; NMR 8H (400 MHz, DMSO) 8.69 (1H, dd, J 1.2, 3.7 Hz), 48 C 49 7.95 (1H, dd, J 1.2, 5.0 Hz), 7.38 (1H, dd, J 3.9, 5.0 Hz), 7.26 (2H, br s), 6.97 (1H, t, J 7.7 Hz), 6.48 - 6.45 (1H, m), 6.44 - 6.40 (1H, m), 6.36 (1H, t, J 1.7 Hz), 5.5 (2H, s) and 5.11 (2H,br s).

1R v~X (Nujol)/crri 13488, 3319, 2952, 1641, 1503 and 1420; NMR 8H (400 MHz, DMSO) 8.49 - 8.42 (1H, m), 8.14 (1H, d, J 1.0 Hz), 7.91 (1H, d, J 3.5 Hz), 7.78 - 7.71 (2H, m), 7.48 - 7.32 (4H, m), 6.88 -6.85 (1H, m), 5.72 (2H, s) and 2.75 (3H, d, J 4.5 Hz).

mp 228.2 - 228.3 C; IR v"~X (DR)/crri 13441, 3318, 3197, 1738, 1648, 1515, 1122, 1006, 888 and 747; NMR 8H (400 MHz, DMSO) 9.45 (1H, s), 9.27 (1H, s), 7.44 (2H, br s), 6.97 (1H, t, J 8.0 Hz), 6.49 - 6.39 (2H, m), 6.35 (1H, s), 5.52 (2H, s), and 5.13 (2H, s).

mp 182.9 -183.1 C; IR v~X (DR)/cni 1 3488, 3311, 3199, 2943, 1611, 1504;

NMR ~H (400 MHz, DMSO) 8.10 (1H, d, J 3.5 Hz), 7.78 (1H, m), 7.01 (1H, t, J

51 N 70 9.0 Hz), 6.79 (1H, dt, J 9.0, 3.5 Hz), 6.75 - 6.73 (1H, m), 6.71 - 6.70 (1H, m), 5.70 (2H, s), 5.38 (2H, br s), 3.71 (3H, s); Anal.
Calcd for C16H13N6OzF ~ 0.1 H20: C, 56.17; H, 3.89, N, 24.56. Found: C, 56.27;
H, 3.85; N, 24.22.

mp 263.8 - 264.0 C; IR v~X (Nujol)/crri 13305, 3192, 1705, 1635 and 1442;

NMR 8H (400 MHz, DMSO) 11.04 (1H, s), 8.37 (1H, d, J4.0 Hz), 8.15 - 8.11 52 p 70 (1H, m), 7.96 (1H, d, J 7.0 Hz), 7.91 (1H, d, J 3.0 Hz), 7.79 (1H, dt, J 7.5, 2.0 Hz), 7.32 (2H, s), 7.18 - 7.11 (1H, m), 6.88 - 6.85 (1H, m) and 5.46 (2H, s).

mp 256.1- 256.4 C; IR v,~X (Nujol)/cni 13454, 3311, 2993, 1664, 1488 and 1439; NMR 8H (400 MHz, DMSO) 8.86 (1H, t, J 6.0 Hz), 8.50 (1H, d, J 4.5 Hz), 53 P 77 8.12 (1H, s), 7.90 (1H, d, J 3.5 Hz), 7.79 (1H, dt, J 7.5, 1.5 Hz), 7.41- 7.25 (4H, m), 6.88 - 6.84 (1H, m) and 5.23 (2H, s), 4.41 (2H, d, J 6.0 Hz); Anal. Calcd for C16H1dN802 ~ 0.25 HZO: C, 54.16; H, 4.12, N, 31.58.
Found: C, 54.01; H, 4.03; N, 31.44.

mp 292.2 - 292.3 C; IR v~x (Nujol)/cni l 3433, 3323, 2975, 2941, 1673 and 1446; NMR 8H (400 MHz, DMSO) 10.50 (1H, s), 8.13 (1H, s), 7.92 (1H, d, J 3.0 Hz), 7.57 (2H, d, J 7.5 Hz), 7.37 - 7.27 (4H, m), 7.08 ( 1H, t, J 7.5 Hz), 6.89 -6.84 (1H, m) and 5,38 (2H, s).

mp 264.5 - 264.8 C;1R v~x (DR)/crn l 4007, 3489, 3308, 3190, 1649, 1552, 1433, 1349, 1227, 1082, 1030 and 729; NMR 8H (400 MHz, DMSO) 5.99 (2H, s), 6.84 - 6.89 (1H, m), 7.39 (2H, s), 7.91 (1H, d, J 3.5 Hz), 8.11- 8.15 (1H, m), 8.59 (2H, d, J 2.0 Hz), 8.78 (1H, t, J 2.0 Hz).

IR v~X (DR)/crri 13508, 3300, 3181, 1611, 1572, 1504, 1420, 1352, 1225 and 1030; NMR 8H (400 MHz, DMSO) 8.22 - 8.16 (2H, m), 7.86 (1H, d, J 3.2 Hz), 7.63 - 7.72 (2H, m), 7.35 (2H, br s), 6.50 (1H, dd, J 1.0, 3.5 Hz), 5.82 (2H, s) and 2.45 (3H, s).

mp 188.8 -188.9 C;1R v~x (Nujol)/crri 1 3492, 3302, 3189, 2951, 1635 and 1505; NMR 8H (400 MHz, DMSO) 8.14 - 8.10 ( 1H, m), 7.90 ( 1H, d, J 3.0 Hz), 7.47 - 7.32 (3H, m), 7.20 (1H, q, J 7.0 Hz), 7.05 (1H, t, J 7.0 Hz), 6.88 - 6.83 (1H, m) and 5.75 (2H, s).

mp 207.0 - 207.4 C; IR v~X (Nujol)/ctri 1 3496, 3229, 3201, 3057, 2965, 2743, 1785 and 1615; NMR 8H (400 MHz, DMSO) 8.13 - 8.10 (1H, m), 7.89 (1H, d, J

3.5 Hz), 7.40 - 7.27 (4H, m), 7.08 (1H, dt, J 8.5, 3.0 Hz), 6.87 - 6.84 (1H, m) and 5.66 (2H, s).

mp 187.9 - 188.7 C IRv~X (DR)/cxri 13338, 3202, 1659,1607, 1567, 1523, 1457, 1424, 1321, 1204 and 1025; NMR 8H (400 MHz, DMSO) 7.88 (1H, d, J

3.5 Hz),7.65 (1H, t, J7.5 Hz), 7.29 (2H, br s), 7.18 (1H, d, J7.5 Hz), 6.89 (1H, d, J 8.0 Hz), 6.51 (1H, d, J 3.0 Hz), 5.69 (2H, s), 2.46 (3H, s) and 2.42 (3H, s);

Anal. Calcd for C16H1sN~0' 0.2 H20:

C, 59.14; H, 4.78, N, 30.17. Found: C, 59.37; H, 4.66; N, 29.86.

mp 209.7 - 209.8 C; IR v~X (DR)/cni 13404, 3330, 3226, 3109, 2961, 2926, 2742, 1637, 1601, 1508, and 1474; NMR bH (400 MHz, DMSO) 7.83 (1H, dd, J

0.5, 3.2 Hz), 7.54 - 7.46 (1H, m), 7.3 (2H, br s), 7.16 (2H, t, J 8.2 Hz), 6.49 (1H, dd, J 1.0, 3.5 Hz), 5.63 (2H,s) and 2.44 (3H, s).

mp 193.8-194.1 C; IR v,I,aX (DR)/crri l 3336, 3218, 2980, 2753, 2432, 1734, 1654, 1611, 1438, 1381, 1331 and 1224; NMR ~H (400 MHz, DMSO) 7.86 (1H, 61 B 20 d, J 3.0 Hz), 7.49 (1H, dd, J 1.5, 5.0 Hz), 7.3 (2H, br s), 7.16 (1H, dd, J 1.0, 3.5 Hz), 7.0 (lH,dd , J 3.5, 5.0 Hz), 6.50 (1H, dd, J 1.0, 3.5 Hz), 5.82 (2H, s) and 2.45 (3H, s).

mp 210.4 - 210.5 C; IR v~X (DR)/ciri 13511, 3300, 3179, 2940, 2740, 2688, 1986, 1832, 1734, 1634, 1500 and 1436; NMR 8H (400 MHz, DMSO) 7.87 (1H, d, J 3.5 Hz), 7.40 - 7.37 (3H, m), 7.30 (2H, br s), 7.23 - 7.18 (1H, m), 6.51 (lH,dd, J 1.0, 5.1 Hz), 5.68 (2H, s) and 2.45 (3H, s).

mp 201.1- 201.2 C; IR v~X (DR)/cni 13453, 3317, 3195, 1638, 1599, 1510 1434; NMR ~H (400 MHz, DMSO) 8.28 (1H, d, J 6.0 Hz), 8.12 - 8.11 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.29 (2H, br s), 6.91 (1H, dd, J 6.0, 2.5 Hz), 6.87 - 6.85 (2H, m), 5.71 (2H, s), 3.81 (3H, s).

mp 218.0 - 218.1 C; IR v",ax (DR)/crri 13999, 3376, 3209, 2916, 2747, 2326, 1957, 1782, 1610, 1515, 1278, 1023 and 763; NMR
SH (400 MHz, DMSO) 2.42 64 B g (3H, s), 5.64 (2H, s), 6.86 (1H, s), 6.91 (1H, d, J 7.5 Hz), 7.13 (1H, t, J 7.0 Hz), 7.17 - 7.26 (2H, m), 7.32 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.12 (1H, s).

mp 208.1- 208.2 C; IR v",aX (Nujol)/cni 1 3347, 3199, 2981, 2932, 2764, 2719, 1660 and 1612; NMR 8H (400 MHz, DMSO) 8.14 - 8.11 (1H, m), 7.90 (1H, d, J

65 B 25 3.5 Hz), 7.41- 7.22 (4H, m), 7.15 - 7.09 (1H, m), 6.87 - 6.83 (1H, m) and 5.69 (2H, s); Anal. Calcd for ClsHloFzN60 ~ 0.5 H20:
C, 53.42; H, 3.29, N, 24.92.

Found: C, 53.72; H, 3.06; N, 24.77.

mp 243.4 - 243.9 C; IR v~x (Nujol)/cni 14008, 3483, 3316, 3196, 1734, 1599 and 1505; NMR 8H (400 MHz, DMSO) 8.32 (1H, dd, J
9.0, 3.0 Hz), 8.21 (1H, d, 66 W 25 J 3.0 Hz), 8.12 - 8.10 (1H, m), 7.68 (1H, d, J 3.5 Hz), 7.31 (1H, d, J 9.0 Hz), 7.00 (2H, s), 6.85 - 6.82 (1H, m), 5.94 (2H, s) and 3.93 (3H, s); Anal. Calcd for C16H1sN~04: C, 52.32; H, 3.57, N, 26.68. Found:
C, 52.16; H, 3.56; N, 26.67.

mp 252.9 - 253.0 C; IR v",aX (DR)/cW 1 3511, 33260, 2945, 1732, 1626, 1573, 1499, 1422, 1327 and 1222; NMR 8H (400 MHz, DMSO) 8.4 (1H, d, J4.5 Hz), 7.87 (1H, d, J 3.0 Hz), 7.77 - 7.71( 2H, m) 7.47 - 7.38 (2H, m), 7.3 (2H, br s), 6.50 (1H, dd, J 1.0, 3.5 Hz), 5.70 (2H, s) , 2.75 (3H, d, J4.5 Hz)and 2.45 (3H, s).

mp 228.1- 229.3 C; IR v",aX (Nujol)/cnri 1 3508, 3263, 2990, 2946, 2837, 1646 68 R 58 and 1419; NMR 8H (400 MHz, DMSO) 8.29 (1H, t, J
6.0 Hz), 8.14 - 8.09 (1H, m), 7.90 (1H, d, J 3.5 H~), 7.33 (2H, s), 7.29 L1H, t, J 7.5 Hz), 7.21- 7.09 (3H, m), 6.88 - 6.83 (1H, m), 5.64 (2H, s), 4.20 (1H, d, J 6.0 Hz) and 1.83 (3H, s);

Anal. Calcd for Cl$H17N~02 ~ 0.25 H20: C, 58.77;
H, 4.79, N, 26.65. Found: C, 58.86; H, 4.54; N, 26.24.

NMR 8H (400 MHz, DMSO) 8.53 (1H, s), 7.69 (1H, s), 7.58 (2H, br s), 7.45 -69 X 2 7.36 (1H, m), 7.29 - 7.22 (2H, m), 7.21 - 7.15 (1H, m) and 5.73 (2H, s);

Retention time 1.14 min.

NMR 8H (400 MHz, DMSO) 8.45 (1H, d, J 5.0, 1.0 Hz), 8.13 - 8.12 (1H, m), 70 N 39 7.91 (1H, dd, J 3.5, 1.0 Hz), 7.51 - 7.48 (2H, m), 7.31 (2H, br s), 6.87 - 6.85 (1H, m), 5.80 (2H, s); Retention time 1.75 min.

mp 228.7 - 228.9 C; IR v,~x (DR)/cni 13408, 3326, 3210, 1648, 1614, 151 l;

NMR SH (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 8.02 - 7.96 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.33 (2H, br s), 7.20 (1H, dd, J 7.5, 2.0 Hz), 7.12 (1H, dd, J 8.0, 2.0 Hz), 6.87 (1H, dd, J 3.5, 1.0 Hz), 5.75 (2H, s);
Anal. Calcd for CIdHmN~OF ~ 0.2 H2O ~ 0.1 C~Hlo02: C, 53.66; H, 3.5?, N, 30.42. Found:
C, 53.68; H, 3.44; N, 30.24.

mp 195.4 - 196.5 C; IR v,I,aX (DR)/crri 13328, 3210, 2956, 2836, 2740, 1736, 1648, 1608, 1438, 1322 and 1250; NMR 8n (400 MHz, DMSO) 7.87 (1H, d, J

72 B 28 3.5 Hz), 7.33 - 7.25 (3H, m), 7.05 (1H, d, J 7.5 Hz), 6.88 (1H, td, J 1.0, 7.5 Hz), 6.87 (1H, dd, J 2.0, 7.5 Hz), 6.50 ( 1H, dd, J 1.0, 3.5 Hz),5.58 ( 2H, s), 3.83 ( 3H, s) and 2.45 (3H, s).

mp 178.7 - 179.3 C; IR v~X (DR)/crri 13468, 3346, 3172, 2988, 2747, 2130, 1943, 1696, 1610, 1418, 1330,and 1177; NMR 8H (400 MHz, DMSO) 7.86 (1H, d, J 3.01 Hz), 7.34 - 7.26 (4H, m), 7.20 - 7.10 (2H, m) 7.09 (lH,s), 6.50 (1H, dd, J 1.0, 3.5 Hz), 5.63 (2H, s), 4.2(2H, d, J 6.0 Hz), 2.45 (2H, s) and 1.34 (9H, s).

mp 214.6 - 215.2 C; IR v",~X (DR)/cni 12877, 1653, 1596, 1523, 1470, 1355, 1284, 1241, 1210 and 1109; NMR 8H (400 MHz, DMSO) 7.87 (1H, d, J 3.0 Hz), 7.16 (1H, t, J 7.0 Hz), 7.0 - 6.75 (3H, m), 6.51 (1H, d , J 3.0 Hz), 5.58 (2H, s) and 2.45 (3H, s).

NMR 8uS400 MHz, DMSO) 4.74 (4H, s), 5.33 (2H, s), 5.62 (2H,. d, J 2.OHz), 75 C 3 5.71 (1H, t, J 2.0 Hz), 6.83 - 6.88 (1H, m), 7.29 (2H, s), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.10 - 8.12 (1H, m); Retention time 2.95 min.

IR v~X (DR)/crri 1 3011, 1650, 1525, 1468, 1351, 1284 and 1210; NMR 8H (400 76 K 100 MHz, CD3OD) 8.36 (1H, d, J 3.5 Hz), 7.53 - 7.42 (4H, m), 6.72 (1H, dd, J 1.0 Hz, 3.5 Hz), 5.76 (2H, s), 4.11 (2H, s) and 2.61 (3H, s).

mp 212.1- 214.3 C; ~ ymax (DR)/cni' 4007, 3474, 3323, 3199, 2934. 2747, 2105, 1647, 1603 1492 1245 1028 and 754 NMR 8H (400 MHz DMSO) 3 82 ~H, s), 5.60 (2H, s~, 6.78 - 6.93 (3H, m), 7.05 (1H, d J 8.5 Hz) 7.24 - 7.38 (3H, m), 7.90 (1H, d, J 3.0 Hz), 8.12 f 1H, s).

IR v,~X (DR)/crri' 4002, 3482, 3313, 3201, 2938, 2739, 2339, 2107, 1936, 1731, 1650, 1436, 1253, 1082 and751; NMR 8n (400 MHz, DMSO) 5.82 (2H, s), 6.84 - 6.88 (1H, m), 7.38 (2H, s), 7.58 (1H, t, J 9.0 Hz), 7.90 (1H, t, J 3.0 Hz), 8.12 (1H, d, J 1.0 Hz), 8.23 - 8.28 (1H, m), 8.29 - 8.35 (1H, m).

mp 308.2 - 308.3 C; IR v~X (DR)/crri 14013, 3456, 3322, 3193, 2958, 2745, 2103, 1861, 1653, 1516, 1237, 1026 and 777; NMR
8H (400 MHz, DMSO) 4.95 (2H, s), 5.56 (2H, s), 6.15 - 6.20 (1H, m), 6.44 - 6.51 (1H, m), 6.84 - 6.93 (2H, m), 7.34 (2H, s), 7.91 (1H, d, J 3.0 Hz), 8.12 (1H, d, J 1.0 Hz).

NMR 8H (400 MHz, DMSO) 8.84 ( 1H, br s), 7.46 -7.35 (2H, m), 7.32 - 7.14 (4H, m) and 5.72 (2H, s); Retention time 0.84 min.

mp 229.3 - 229.4 C; IR v,~X (DR)/cxri 1 3514, 3292, 3166, 1614, 1503; NMR ~H

(400 MHz, DMSO) 7.88 - 7.84 (2H, m), 7.47 (1H, d, J 8.0 Hz), 7.31 (2H, br s), 81 B 47 7.22 (1H, d, J 7.0 Hz), 6.52 - 6.51 (1H, m), 5.75 (2H, s), 2.46 (3H, s); Anal.

Calcd for CISHizN~OCI ~ 0.1 H20: C, 52.44; H, 3.58, N, 28.54. Found: C, 52.62;

H, 3.59; N, 28.20.

mp 205.0 - 205.3 C; NMR 8H (400 MHz, DMSO) 7.97 - 7:85 (5H, m), 7.46 82 H 36 7.41 (3H, m), 7.32 (2H, br s), 7.13 (1H, d, J 8.5 Hz), 6.53 - 6.52 (1H, m), 5.85 (2H, s), 2.46 (3H, s).

mp 252.8 - 253.3 C; NMR SH (400 MHz, MeOD) 8.21 (lH~~d, J 3.0 Hz), 7.98 83 C 19 (1H, d, 3.5 Hz), 7.62 - 7.52 (2H, m), 7.37 - 7.31 (2H, m) and 5.81 (2H, s);

Retention time 0.83 min.

mp 235.8 - 236.5 C; IR v~X (DR)/crri 1 3309, 2836, 2033, 1823, 1651, 1505, 84 C 53 1468, 1354, 1250 and 1209 ; NMR 8n (400 MHz,CD30D) 8.18 (1H, d, J4.0 Hz), 7.47 - 7.37 (3H, m), 6.61 (1H, dd, J 1.0, 3.5 Hz), 5.82 (2H, s) and 2.57 (3H, s).

mp 215.9 - 217.5 C;1R v,r,ax (Nujol)/cni l 3308, 2955, 2869, 1634, 1505 and 1435; NMR 8H (400 MHz, DMSO) 8.27 (1H, t, J 5.5 Hz), 8.13 (1H, d, J 1.0 Hz), 85 R 72 7.91 (1H, d, J 3.5 Hz), 7.36 (2H, s), 7.31 (1H, t, J 7.5 Hz), 7.17 (2H, t, J 7.5 Hz), 7.09 (1H, s), 6.89 - 6.84 (1H, m), 5.64 (2H, s), 4.21 (2H, d, J 6.0 Hz), 1.93 (2H, s) and 0.79 (6H, d, J 6.5 Hz).

NMR 8H (400 MHz, DMSO) 8.84 (1H, d, J 5.5 Hz), 8.14 (1H, d, J 2.0 Hz), 8.08.

86 B 51 (1H, dd, J 5.5, 1.0 Hz), 7.89 (1H, d, J 5.5 Hz), 7.34 (2H, br s), 6.53 - 6.52 (1H, m), 5.98 (2H, s), 2.46 (3H, s); Retention time 1.85 min.

NMR ~H (400 MHz, DMSO) 9.10 (1H, s), 8.69 (1H, s), 8.05 (1H, d, J 5.5 Hz), 7.89 (1H, d, J 3.0 Hz), 7.32 (2H, br s), 6.59 - 6.57 (1H, m), 6.53 - 6.51 (1H, m), 6.37 - 6.36 (1H, m), 5.60 (2H, s), 2.46 (3H, s);
M/Z 339 (M+H)+; Retention time 0.79 min.

mp 258.8 - 259.0 C; lR v~x (DR)/crri l 4014, 3316, 3204, 2966, 2746, 2561, 2106, 1962, 1606, 1526, 1436, 1351, 1029 and 758;
NMR 8H (400 MHz, DMSO) 246 (3H, s), 5.79 (2H, s), 6.86 - 6.88 (1H, m), 7.23 (1H, d, J 7.5 Hz), 7.30 -7.50 (3H, m), 7.81 (1H, d, J 8.0 Hz), 7.91 (1H, d, J 3.5 Hz), 8.13 - 8.15 (1H, m).

Anal. Calcd for C16H13N7~3 C, 54.70; H, 3.73; N, 2.7.89. Found: C, 54.70; H, 3.77; N, 27.48.

mp 247.1- 247.2 C; IR v~X (DR)/crri 13322, 1740, 1600, 1240, 1167, 959 and 770' NMR 8H (400 MHz, DMSO) 2.10 (3H, s), 4.93 (2H, s), 5.56 (2H, s), 6.11 (lH,d,J6.5Hz),6.58(lH,d,J8.OHz),6.80(lH,t,J7.5Hz),6.85-6.87(1H, m), 7.35 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.12 -8.14 (1H, m).

mp 268.5 - 269.1 C; IR v~X (DR)/crri 14010, 3451, 3317, 3182, 2957, 2749, 2104, 1844, 1652, 1608, 1487, 1335, 1025 and 764;
NMR 8H (400 MHz, DMSO) 1.99 (3H, s), 4.89 (2H, s), 5.47 (2H, s), 6.36 -6.43 (2H, m), 6.84 - 6.89 (2H, m), 7.35 (2H, s), 7.91 (1H, d, J 3.5 Hz) 8.12 - 8.14 (1H, m).

mp 284.3-284.5 C; IR v~X (DR)/cni 13321, 3216, 1612, 1031, 765 and 552;

91 B 15 NMR SH (400 MHz, DMSO) 8.12 (1H, d, J 1.0 Hz), 7.88 (1H, d, J 3.5 Hz), 7.35 (2H, br s), 6.85 (1H, dd, J3.5, 1.5 Hz), 5.44 (2H, s), 2.52 (3H, s) and 2.25 (3H, s) mp 267.9 - 268.5 C; NMR 8H (400 MHz, DMSO) 2.32 (3H, s), 5.69 (2H, s), 92 B 8 6.85 - 6.89 (1H, s), 7.04 - 7.10 (1H, m), 7.33 -7.54 (4H, m), 7.90 (1H, d, J 3.5 Hz), 8.13 - 8.15 (1H, m).

IR v~X (Nujol)/crri 13316, 3193, 2926, 2851, 1637, 1508 and 1437; NMR 8H

(400 MHz, DMSO) 8.11- 8.09 (1H, m), 7.89 (1H, dd, J 3.5, 1.0 Hz), 7.27 (2H, s), 6.86 - 6.83 ( 1H, m), 4.26 (2H, d, J 7.5 Hz), 2.04 -1.90 ( 1H, m), 1.72 -1.50 (5H, m) and 1.25 - 0.95 (5H, m).

mp 237.8 - 238.0 C; NMR ~H (400 MHz, DMSO) 2.49 (3H, s), 5.76 (2H, s), 6.84 - 6.88 (1H, m), 7.28 (1H, dd, J 8.5, 1.5 Hz), 7.30 - 7.42 (3H, m), 7.91 (1H, d, J 3.5 Hz), 7.97 (1H, d, J 8.5 Hz), 8.11- 8.14 (1H, m). Anal. Calcd for C16H13N7o3 ' 0.1 HZO: C, 54.42; H, 3.77; N, 27.77.
Found: C, 54.73; H, 3.78; N, 27.40.

mp 249.8 - 250.0 C;1R v",aX (DR)/crri 1 3437, 3317, 3210, 2964, 2865, 1610, 1508; NMR SH (400 MHz, DMSO) 8.19 - 8.17 (1H, m), 8.1.2 (1H, m), 7.92 - 7.91 (1H, m), 7.66 - 7.63 (1H, m), 7.24 - 7.20 (3H, m), 6.86 (1H, dd; J 3.5, 1.5 Hz), 5.80 (2H, s), 2.44 (3H, s).

mp 226.6 - 226.9 C; NMR 8H (400 MHz, DMSO) 2.32 (3H, s), 5.98 (2H, s), 96 B 4 6.84 (1H, s), 6.85 - 6.90 (1H, m), 7.35 (2H, s), 7.43 (1H, d, J 7.5 Hz), 7.91 (1H, d, J 7.5 Hz), 8.07 - 8.15 (2H, m).

mp 245.3 - 246.1 C; IR v",~,~ (DR)/cnri 14010, 3406, 3320, 3198, 2929, 2746, 1608, 1507, 1414, 1285, 1022 and 753; NMR 8H (400 MHz, DMSO) 2.00 (3H, s), 4.86 (2H, s), 5.42 (2H, s), 6.54 (1H, d, J 8.0 Hz), 6.82 - 6.85 (1H, m), 6.90 (1H, dd, J 8.0, 2.0 Hz), 6.92 - 6.95 (1H, m), 7.29 (2H, s), 7.88 (1H, d, J 3.5 Hz), 8.09 - 8.12 (1H, m). Anal. Calcd for Cl6HisN~O ~
0.2 H20: C, 59.14; H, 4.78; N, 30.17. Found: C, 59.44; H, 4.74; N, 29.82.

IR vt"aX (Nujol)/crri' 3324, 3206, 1698, 1650 and 1611; NMR 8H (400 MHz, 98 O 98 DMSO) 13.56 - 12.46 (1H, s), 8.13 - 8.11 (1H, s), ~ 7.92 - 7.84 (3H, m), 7.56 -7.31 (3H, m), 6.87 - 6.85 (1H, m) and 7.74 (2H, s).

IR v~X (Nujol)/cni 1 3324, 1644, 1491 and 1417;
NMR 8H (400 MHz, DMSO) 99 P 66 8.12 (1H, s), 7.98 - 7.93 (1H, s), 7.91 (1H, d, J 3.0 Hz), 7.81 (1H, d, J 6.5 Hz), 7.77 (1H, s), 7.47 - 7.29 (5H, m), 6.86 (1H, s) and 5.77 - 5.68 (2H, m).

mp 285.7-285.9 C; lR v~X (DR)/crri 13345, 3197, 1664, 1613, 1116, 766 and 100 B 13 600; NMR 8H (400 MHz, DMSO) 8.13 - 8.02 (1H, m) 7.90 (1H, d, J 3.5 Hz), 7.37 - 7.27 (3H, m), 6.86 (1H, dd, J 3.5, 2.0 Hz), 5.67 (2H, s) and 2.52 (3H, s).

mp 279.9-280.3 C; NMR 8H (400 MHz, DMSO) 8.33 (3H, br s), 7.93 (1H, d, J

101 AA 32 2.0 Hz), 7.51 - 7.39 (2H, m), 7.39 - 7.31,(3H, m), 5.69 (2H, s) and 3.98 (2H, q, J

5.5 Hz).

1R v",aX (Nujol)/crri 1 3480, 3322, 3202, 283, 1608 and 1506; NMR ~n (400 MHz, DMSO) 8.12 (1H, s), 7.90 (1H, d, J 3.5 Hz), 7.47 102 - 7.25 (5H, m), 6.87 -6. 84 (1H, m), 5.72 (2H, s), 3.77 - 3.61 (1H, s), 2.76 (3H, s), 1.10 (3H, s) and 0.99 (3H, s).

1R v,~X (Nujol)/crri 13298, 2972, 1635 and 1418;
NMR 8H (400 MHz, DMSO) 8.21 (1H, d, J 7.5 Hz), 8.12 (1H, s), 7.91 (1H, d, J 3.0 Hz), 7.82 - 7.74 (2H, m), 7.48 - 7.29 (4H, m), 6.86 (1H, s), 5.71 (2H, s), 4.13 - 4.01 (1H, m) and 1.13 (6H, d, J 6.5 Hz).

mp 249.9 - 250.5 C; NMR SH (400 MHz, DMSO) 2.07 (3H, s), 5.06 (2H, s), 5.43 (2H, s), 6.60 - 6.65 (2H, m), 6.81- 6.89 (2H, m), 7.37 (2H, s), 7.90 (1H, dd, J 3.5, 1.0 Hz), 8.12 (1H, d, J 1.0 Hz). Anal. Calcd for Cl6HISN~O ~ 0.2 H20: C, 59.14; H, 4.78; N, 30.17. Found: C, 59.53; H, 4.75;
N, 29.87.

mp 263.2 - 263.5 C; IR vt"ax (DR)/cni' 3499, 3307, 3192, 2958, 2238, 1610, 1490; NMR sH (400 MHz, DMSO) 8.73 (1H, d, J 5.0 Hz), 8.13 - 8.12 (1H, m), 7.92 - 7.90 (1H, m), 7.85 - 7.81 (2H, m), 7.30 (2H, br s), 6.87 - 6.86 (1H, m), 5.87 (2H, s).

mp 288.1-288.2 C; IR v",~x (DR)/crri 1 3324, 3196, 1609, 1489, 1166, 1004, 798 and 550; NMR 8H (400 MHz, DMSO) 8.59 (1H, s), 8.44 (1H, s), 8.12 (1H, s), 7.90 (1H, d, J 3.5 Hz), 7.31 (2H, br s), 6.86 (1H, dd, J 3.5, 1.5 Hz), 5.81 (2H, s) and 2.48 (3H, s).

mp 276.4-277.4 C; IR v,~x (DR)/cni' 3443, 3324, 3202, 1610, 1324, 1229, 1030 and 788; NMR SH (400 MHz, DMSO) 9.01 (1H, dd, J4.0, 2.0 Hz), 8.45 (1H, dd, 107 B 22 J 8.5, 2.0 Hz), 8.14 - 8.12 (1H, m), 7.97 (1H, d, J 8.0 Hz), 7.93 (1H, d, J 3.5 Hz), 7.64 (1H, 1H, dd, J 8.5, 4.0 Hz), 7.52 (1H, t, J
7.0 Hz), 7.31 (2H, br s), 7.15 (1H, d, J 7.5 Hz), 6.87 ( 1H, dd, J 3.5, 2.0 Hz) and 6.31 (2H, s).

mp 215.0-215.3 C; IR v~x (DR)/crri' 3325, 3198, 1612, 1246, 1026, 727 and 567; NMR 8H (400 MHz, DMSO) 8.14 - 8.12 (1H, m), 7.91 (1H, dd, J 3.5, 1.0 Hz), 7.90 - 7.85 (2H, m), 7.52 (1H, s), 7.51 - 7.46 (3H, m), 7.36 (2H, br s), 6.86 (1H, dd, J 3.5, 1.5 Hz), and 5.81 (2H, s).

mp 289.8-289.9 C;1R v~X (DR)/cxri 1 3350, 2924, 2863, 1981, 1723, 1618, 109 Q 23 1351, 1100, 974, 766 and 524; NMR 8H (400 MHz, DMSO) 8.23 - 8.16 (2H, m), 7.77 - 7.62 (3H, m), 7.49 (2H, br s), 5.88 (2H, s) and 2.56 (3H, s).

mp 247.4 - 247.5 C; IR v~X (DR)/crli l 3999, 3470, 3316, 3198, 2929, 2744, 2345, 2103, 1924, 1837, 1773, 1649, 1435, 1355, 1237, 1029 and 768; NMR SH

(400 MHz, DMSO) 5.79 (2H, s), 6.85 - 6.87 (1H, m), 7.36 (2H, s), 7.56 (1H, dd, J 8.5, 2.0 Hz), 7.76 (1H, d, J 8.0 Hz), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.04 (1H, d, J

2.0 Hz), 8.12 - 8.13 (1H, m). Anal. Calcd for ClsHioN~03C1:
C, 48.47; H, 2.71;

N, 26.36. Found: C, 48.63; H, 2.80; N, 26.22.

mp 244.1- 244.6 C; NMR bH (400 MHz, DMSO) 5.84 (2H, s), 6.85 - 6.89 (1H, m), 7.37 (2H, s), 7.54 (1H, dd, J 9.5, 1.5 Hz), 7.84 (1H, t, J 1.0 Hz), 7.92 111 B 14 (1H, d, J 3.5 Hz), 8.08 (1H, dd, J 9.0, 1.0 Hz), 8.12 - 8.15 (1H, m). Anal. Calcd for C15H1oN$OZ ' 0.75 C3H~N0: C, 53.25; H, 3.95;
N, 31.50. Found: C, 53.08; H, 3.79; N, 31.38.

mp 190.4 - 191.4 C; IR v,;,aX (DR)/cmi 1 3482, 3308, 3194, 2940, 2880, 1610, 1508; NMR ~H (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.78(lH,t,JB.OHz),7.35-7.32(3H,m),7.04(lH,d,J7.5Hz),6.86(lH,dd,J

3.5, 2.0 Hz), 5.75 (2H, s), 4.43 (2H, s), 3.33 (3H, s).

IR v~x (Nujol)/cxri 1 3499, 3316, 3193, 2946, 1651 and 1509; NMR 8H (400 MHz, DMSO) 8.13 - 8.10 (1H, m), 7.90 (1H, d, J 3.5 Hz), 7.39 - 7.26 (7H, m), 6.87 - 6.84 (1H, m) and 5.67 (2H, s); Anal. Calcd for ClSHizNsO ~ 0.75 HzO: C, 58.91; H, 4.45, N, 27.48. Found: C, 58.84; H, 4.10;
N, 27.32.

mp 256.7 - 257.1 C; IR v",aX (DR)/crri 14003, 3452, 3324, 3203, 2950, 2746, 2102, 1733, 1654, 1516, 1420, 1305, 1221, 1106, 1024 and 761; NMR 8H (400 MHz, DMSO) 5.38 (2H, s), 5.51 (2H, s), 6.46 (1H, dd, J 8.5, 2.5 Hz), 6.58 (1H, d, J 2.0 Hz), 6.84 - 6.87 (1H, m), 7.15 (1H, d, J 8.0 Hz), 7.32 (2H, s), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.11- 8.13 (1H, m). Anal. Calcd for C15H12N70C1 ~ 0.3 H20:

C, 51.90; H, 3.66; N, 28.24. Found: C, 52.12; H, 3.48; N, 27.86.

NMR ~H (400 MHz, DMSO) 8.84 (1H, d, J 5.5 Hz), 8.15 - 8.12 (2H, m), 8.08 -115 B 12 8.06 (1H, m), 7.92 - 7.91 (1H, m), 7.32 ( 2H, br s), 6.87 (1H, dd, J 3.5, 1.5 Hz), 5.99 (2H, s); Retention time 1.28 min.

NMR bH (400 MHz, DMSO) 9.08 (1H, br s), 8.66 (1H, br s), 8.13 - 8.12 (1H, m), 116 Z 87 8.06 - 8.04 (1H, m), 7.93 - 7.91 (1H, m), 7.32 (2H, br s); 6.87 - 6.86 (1H, m), 6.60 - 6.58 (1H, m), 6.38 - 6.37 (1H, m), 5.61 (2H, s); M/Z 325 (M+H)~.

IR v~X (DR)/cni' 3491, 3310, 3198, 2976, 1612; NMR
8H (400 MHz, DMSO) 117 B 9 8.14-8.13(lH,m),7.99-7.98(lH,m),7.93-7.91(lH,m),7.80-7.79(1H, m), 7.34 (2H, br s), 6.88 - 6.86 (1H, m), 5.90 (2H, s), 2.57 (3H, s).

NMR 8H (400 MHz, DMSO) 13.45 (1H, br s), 9.50 (1H, br s), 8.15 - 8.14 (1H, 118 Z 91 m), 7.92 (1H, d, J 3.5 Hz), 7.39 (2H, br s), 6.87 - 6.86 (1H, m), 6.56 (1H, br s), 6.15 (1H, br s), 5.67 (2H, s), 2.39 (3H, s); M/Z
339 (M+H)+.

mp >230 C; IR v~X (DR)/crri 13993, 3509, 3314, 3195, 2997, 2950, 2682, 119 B 15 2561, 2101, 1943, 1780, 1613, 1501, 1433, 1345, 1100, 1027, 889 and 780;

NMR 8H (400 MHz, DMSO) 6.00 (2H, s), 6.85 - 6.90 (1H, m), 7.05 (1H, d, J 8.5 Hz), 7.37 (2H, s), 7.78 (1H, dd, J 8.5, 2.0 Hz), 7.91 (1H, d, J 3.5 Hz), 8.14 (1H, d, J 1.0 Hz), 8.27 (1H, d, J 2.5 Hz). Anal. Calcd for CISHioN~~3C1 ~ 0.3 HzO: C, 47.77; H, 2.83; N, 26.00. Found: C, 47..65; H, 2.71;
N, 25.85.

mp 211.4 - 211.6 C; IR v,r,ax (DR)/cW 14015, 3325, 3218, 2969, 2878, 2101, 1653, 1508, 1423, 1275, 1023, 834 and 761; NMR 8H
(400 MHz, DMSO) 5.45 (2H, s), 5.60 (2H, s), 6.51 ( 1H, dd, J 8.0, 2.0 Hz), 6.70 - 6.79 (2H, m), 6.83 -6.89 (1H, m), 7.38 (2H, s), 7.90 (1H, d, J 3.5 Hz), 8.12 (1H, s).

mp 292.3-292.4 C; IR v~X (DR)/czri 13324, 3207, 2098, 1602, 1527, 1352, 1024 and 813; NMR 8H (400 MHz, CDCl3) 8.10 (1H, d, J 3.0 Hz), 7.79 (1H, d, J 1.5 Hz), 7.64 (2H, d, J 8.5 Hz), 7.49 (2H, d, J 8.5 Hz), 6.71 (1H, dd, J 3.5, 1.5 Hz), 5.71 (2H, s) and 5.38 (2H, br s). ' ' mp 227.5 - 228.5 C; IR v~X (DR)lcni 1 , 3265, 1701, 1521, 1480, 1413, 1355, 1309, 1204 and 1147; NMR 8H (400 MHz, DMSO) 8.11 (1H, d, J 1.0 Hz), 7.9 122 A 50 1H, d, J 3.5 Hz), 7.3 (2H, br s), 7.04 (1H, d, J
2.0 Hz), 6.90 ( 1H, d, J 8.0 Hz), 6.85 (.1H, dd, J 1.5, 3.5 Hz), 6.79 ( 1H, dd, J 2.0, 8.0 Hz), 5.57 (2H, s), 3.71 (3H, s,) and 3.72 ( 3H, s).

mp 214.6 - 216.2 C; IR v,r,aX (DR)/crri 13512, 3295, 3173, 2988, 2736, 2415, 1636, 1437,1340 and 1228; NMR 8H (400 MHz, DMSO) 7.97 (1H, d, J 8.5 Hz), 7.87(1H, d, J 3.0 Hz), 7.40 (1H, d, J 1.0 Hz), 7.31 (2H, br s), 7.27(1H, dd, J 1.5, 8.0 Hz), 6.51 (1H, dd, J 1.0, 3.5 Hz), 5.74 (2H,s), 2.48 ( 3H, s) and 2.46 (3H, s).

mp 215.7- 216.7 C; IR v",ax (DR)/cni 13328, 2928, 2424, 2345, 1609 and 1263;

NMR SH (400 MHz, DMSO) 7.85 (1H, d, J 3.5 Hz), 7.26 (2H, br s), 6.93 (1H, d, Jl.SHz),6.89(lH,dd,J2.0,8.0Hz),6.54(lH,d,J8.0Hz),6.49(1H,J1.0,3.5 Hz ), 5.40 (2H, s), 4.89 (2H, br s), 2.45 (3H, s) and 2.27 (3H, s).

mp 221.5 - 221.6 C; IR v~X (DR)lcrri 13506, 3294, 3178, 2683, 1613, 1315, 1027 and 697; NMR 8H (400 MHz, DMSO) 8.13 - 8.11 (1H, m), 7.90 (1H, d, J

4.5 Hz), 7.38 (2H, br s), 6.86 (1H, dd, J 3.5, 1.5 Hz), 6.18 - 6.16 (1H, m), 5.70 (2H, s) and 2.36 (3H, s).

mp 229.6 - 230.3 C;1R v~X (DR)/crri 13317, 3198, 1602, 1499; NMR 8H (400 MHz, DMSO) 8.44 - 8.43 (1H, m), 8.31 (1H, d, J 5.0 Hz), 8.14 - 8.13 (1H, m), 7.92 (1H, d, J 3.0 Hz), 7.35 (2H, br s), 6.88 - 6.86 (1H, m), 6.70 (1H, d, J 5.0 Hz), 5.71 (2H, s), 2.39 (3H, s).

mp 275.0-273.3 C;1R v~X (DR)lcrri 13449, 3310, 3202, 1605, 1487, 1420, 127 B 13 1023, 836, 760 and 551; NMR SH (400 MHz, DMSO) 8.15 - 8.11 (1H, m), 8.07 (1H, d, J 9.0 Hz), 7.91 (1H, d, J 3:5 Hz), 7.68 (1H, dd, J 9.0, 6.5 Hz), 7.38 - 7.29 (3H, m), 6.86 (1H, dd, J 3.5, 1.5 Hz) and 6.15 (2H, s).

mp 129.1-131.0 C; IR v"~X (DR)icni 13993, 3470, 3310, 3197, 1610, 1508 1420, 1239, 1002 and 796; NMR 8H (400 MHz, DMSO) 8.74 (1H, d, J 1.5 Hz), 8.61(lH,d,J2.5Hz),8.57-8.54(lH,m),8.13-8.11(lH,m),7.91(lH,d~J

3.5 Hz), 7.31 (2H, br s), 6.86 (1H, dd, J 3.5, 2.0 Hz) and 5.88 (2H, s).

mp 266.5 - 266.7 C; IR v~x (DR)/cni 1 4018, 3487, 3310, 3193, 2744, 1636, 1585, 1539, 1507, 1437, 1347, 1266, 1238 and 1196 ; NMR 8H (400 MHz, 129 B 20 DMSO) 8.15 (1H, dd, J 2.5, 7.5 Hz), 8.12 (1H, d, J 1.0 Hz), 7.90 ( 1H, d, J 3.5 Hz), 7.73 -7.68 (1H, m), 7.58 (1H, dd, J 11.3, 8.8 Hz), 7.36(2H, br s), 6.88 (1H, dd, J 1.5, 3.5Hz) and 5.78 (2H, s).

mp 149.0 - 149.6 C; 1R v",aX (DR)!cW 14072, 3332, 3198, 1654, 1604, 1348, 1237, 1111, 1012, 775, 691 and 570; NMR 8H (400 MHz, DMSO) 8.79 - 8.70 (2H, m), 8.25 - 8.14 (2H, m), 7.77 - 7.58 (5H, m), 7.38 (2H, br s) and 5:87 (2H, s).

mp 225.7 - 225.8 C; NMR 8H (400 MHz, DMSO) 8.33 ( 1H, d, J 4.5 Hz), 8.13 -8.12 (1H, m), 7.92 - 7.91 (1H, m), 7.30 (2H, br s), 7.15 (1H, d, J 5.0 Hz), 7.07 -131 B 22 7.06 (1H, m), 6.86 (1H, dd, J 1.5, 3.5 Hz), 5.72 (2H, s), 2.28 (3H, s); Anal. Calcd for C15H13N~0 ~ 0.7 H20: C, 56.31; H, 4.54, N, 30.65.
Found: C, 56.57; H, 4.24;

N, 30.33.

IR vt"aX (DR)/crri 13332, 2977, 1694, 1608; NMR
8H (400 MHz, DMSO) 8.41 (1H, d, J 4.5 Hz), 8.14 - 8.13 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.43 (1H, t, J 6.0 Hz), 7.33 (2H, br s), 7.16 (1H, d, J 4.5 Hz), 6.97 - 6.96 (1H, m), 6.87 (1H, dd, J

2.0, 3.5 Hz), 5.76 (2H, s), 4.10 (2H, d, J 6.0 Hz), 1.31 (9H, s).

mp 209.7 - 209.9 C; IR v""~X (Nujol)/crri 1 3506, 3311, 3196, 2996, 2951, 1637, 1518 and 1283; NMR 8u (400 MHz, DMSO) 8.15 - 8.12 133 B 14 (1H, m), 7.91 (1H, dd, J 3.5, 1.0 Hz), 7.84 (1H, d, J 8.0 Hz), 7.43 (1H, d, J 1.5 Hz), 7.42 - 7.35 (2H, s), 6.88 - 6.82 (2H, m), 5.77 (2H, s) and 3.91 (3H, s).

mp 240.9 - 241.1 C. IR v",aX (DR)/crn 14010, 3629, 3499, 3313, 3196, 2946, 2733, 2447, 1943, 1638, 1528, 1420, 1351, 1222, 1025 and 960. NMR ~H (400 MHz, DMSO) 5.85 (2H, s), 6.84 - 6.89 (1H, m), 7.36 (2H, s), 7.50 (2H, dt, J 8.5, 2.0 Hz), 7.92 (1H, dd, J 3.5, 1.0 Hz), 8.12 - 8.14 (1H, m), 8.22 (2H, dt, J 9.0, 2.0 Hz). Anal. Calcd for C15H11N~03 ~ 0.6H20: C, 51.75;
H, 3.53; N, 28.17. Found:

C, 52.08; H, 3.22; N, 27.96.

mp 208.6 - 208.8 C; 1R v~X (DR)/crri 13432, 3304, 3191, 2961, 1616, 1500, 1434; NMR SH (400 MHz, DMSO) 8.14 - 8.13 (1H, m), 7.93 - 7.91 (1H, m), 7.67 (1H, t, J 7.5 Hz), 7.35 (2H, br s), 7.19 (1H, d, J 7.5 Hz), 6.90 - 6.86 (2H, m), 5.73 (2H, s), 2.68 (2H, q, J 7.5 Hz), 1.14 (3H, t, J
7.5 Hz).

mp 172.7 -173.2 C; NMR 8H (400 MHz, DMSO) 8.42 (1H, d, J 5.5 Hz), 8.14 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.39 (2H, br s), 7.11 - 7.10 (1H, m), 6.97 (1H, d, J 5.5 Hz), 6.87 (1H, dd, J 2.0, 3.5 Hz), 5.70 (2H, s), 2.71 (2H, q, J 7.5 Hz), 1.18 (3H, t, J 7.5 Hz).

mp 176.3 - 176.5 C; IR v~"aX (DR)/cmi 13452, 3326, 3209, 2973, 1734, 1611, 1328, 1026 and 774; NMR 8H (400 MHz, DMSO) 8.13 (1H, d, J 2.5 Hz), 7.90 137 B 13 (1H, d, J 3.5 Hz), 7.72 (1H, d, J 3.5 Hz), 7.61 (1H, d, J 8.5 Hz), 7.34 (2H, br s), 7.19 (1H, t, J 8.0 Hz), 6.86 (1H, dd, J 3.5, 2.0 Hz), 6.77 (1H, d, J 4.0 Hz), 6.75 .

(1H, d, J7.5 Hz), 6.07 (2H, s) and 1.54 (9H, s).

mp 58.5 - 62.6 C; IR V~x (DR)/crri 1 3430, 3315, 3210, 3973, 1718, 1165, 834 and 772; NMR 8H (400 MHz, DMSO) 8.13 - 8.11 (1H, m), 8.03 (1H, d, J 8.0 138 B 26 Hz), 7.89 (1H, d, J3.5 Hz), 7.73 (1H, d, J4.0 Hz), 7.39 (2H, br s), 7.30 (1H, t, J

8.5 Hz), 7.08 (1H, d, J 7.0 Hz), 6.91 (1H, d, J
4.5 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz), 5.90 (2H, s) and 1.62 (9H, s).

mp 192.3 - 193.5 C; NMR 8H (400 MHz, DMSO) 11.27 (1H, br s), 8.12 (1H, d, 139 K 85 J 2.5 Hz), 7.90 (1H, d, J 3.5 Hz), 7.39 - 7.33 (2H, m), 7.04 (1H, t, J 8.0 Hz), 6.87 - 6.83 (2H, m), 6.56 - 6.52 (1H, m) and 5.86 (2H, s).

mp 184.0 -185.2 C; IR v~X (DR)/cni 1 3638, 3462, 3331, 3184, 2976, 1686, 1174, 1026 and 756; NMR bH (400 MHz, DMSO) 8.13 (1H, d, J 1.0 Hz), 7.90 (1H, d, J 3.5 Hz), 7.45 - 7.31 (3H, m), 7.27 - 7.17 (4H, m), 6.86 (1H, dd, J 3.5, 2.0 Hz), 5.64 (2H, s), 4.08 (2H, d, J 6.0 Hz) and 1.37 (9H, s).

mp 240.3 - 240.4 C. IR v~X (DR)/cni 13320, 3198, 2929, 1610, 1505, 1438, 1280, 1233, 1028, 956 and 759; NMR sH (400 MHz, DMSO) 5.85 (2H, s), 6.84 -6.89 (1H, m), 7.36 (2H, s); 7.50 (2H, dt, J 8.5, 2.0 Hz), 7.92 (1H, dd, J 3.5, 1.0 Hz), 8.12 - 8.14 (1H, m), 8.22 (2H, dt, J 9.0 Hz).

mp 189.0 -189.1 C;1R v~X (DR)/crri 13506, 3304, 3180, 1735, 1609, 1167, 1029 and 766; NMR SH (400 MHz, DMSO) 8.15 -8.11 (1H, m), 8.02 (1H, d, J

142 B 14 8.5 Hz), 7.91 (1H, d, J 3.5 Hz), 7.68 (1H, d, J
3.5 Hz), 7.53 (1H, s), 7.37 (2H, br s), 7.29 (1H, dd, J 8.5, 1.5 Hz), 6.86 (1H, dd, J 3.5, 2.0 Hz), 6.70 (1H, d, J 3.5 Hz), 5.75 (2H, s) and 1.61 (9H, s).

mp 167.0 - 167.3 C; IR v~X (DR)/crri 13650, 3485, 3320, 3194, 2978, 1726, 1168, 953 and 756; NMR 8H (400 MHz, DMSO) 9.00 (1H, br s), 8.13 (1H, s), 143 B 18 7.91(lH,d,J3.5Hz),7.57(lH,t,JB.OHz),7.39(2H,brs),7.16(lH,d,J11.5 Hz), 7.04 (1H, d, J 8.5 Hz), 6.86 (1H, dd, J 3.5, 2.0 Hz), 5.64 (2H, br s) and 1.44 (9H, s).

mp >300 C dec; IR v",aX (DR)/ciri 12903, 2030, 1606, 1464, 1033, 779 and 589;

NMR 8H (400 MHz, DMSO) 8.30 (2H, br s), 8.14 (1H.
s), 7.92 (1H, d, J 3.5 Hz), 7.46 (2H, d, J 8.0 Hz), 7.32 (2H, d, J 8.0 Hz), 6.92 - 6.84 (1H, m), 5.69 (2H, s) and 4.04 - 3.96 (2H, m).

1R v~x (DR)lcrri 1 3511, 3292,3164,2971, 1609, 1525, 1437, 1354 and 1239;

~ sH (400 MHz, DMSO) 8.19 (2H, m), 7.90 (1H, d, J
3.5 Hz), 7.72 - 7.64 (2H, m), 7.36 (2H, br s), 6.53 (1H, d, J 3.5 Hz), 5.83 (2H, s), 2.80 (2H, q, J 7.5 Hz) and 1.27 (3H, t, J 7.5 Hz).

mp 180.0 - 180.5 C;1R vI"aX (DR)/cW 13325, 3206, 2976, 1734, 1604, 1341, 1024 and 768; NMR 8H (400 MHz, DMSO) 7.92 (1H, d, J 3.0 Hz), 7.84 (1H, s), 146 B 35 7.67 (1H, d, J 4.0 Hz), 7.62 (1H, d, J 8.0 Hz), 7.37 (2H, br s), 7.26 (1H, d, J 8.0 Hz), 6.87 (1H, dd, J 3.5, 1.5 Hz), 6.70 (1H, d, J
3.5 Hz), 5.80 (2H, s) and 1.51 (9H, s).

mp >200 C dec; IR v~X (DR)/cni 12816, 2004, 1660, 1507, 1427, 1277, 1030, 746 and 524; NMR 8n (400 MHz, DMSO) 8.15 - 8.12 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.14 (1H, d, J 12.0 Hz), 7.06 - 6.94 (2H, m), 6.86 (1H, dd, J 3.5, 2.0 Hz) and 5.57 (2H, s).

Mp 259.8 - 259.9 C. IR v",aX (DR)/crri 13382, 3214, 2986, 2731, 2090, 1767, 1730, 1606, 1487, 1372, 1275, 1137, 1029, 873 and 771; NMR 8H (400 MHz, DMSO) 1.49 (9H, s), 5.63 (2H, s), 6.85 - 6.86 (1H, rn), 7.20 - 7.27 (2H, m), 7.40 (2H, s), 7.87 (1H, d, J 3.0 Hz), 8.11- 8.14 (1H, m).

IR v",aX (Nujol)/cni 1 3375, 3061, 1653, 1509 and 1474; NMR bH (400 MHz, DMSO) 11.15 - 10.13 (1H, s), 8.43 - 7.36 (3H, s), 8.14 - 8.12 (1H, m), 7.89 (1H, dd, J 3.5, 1.0 Hz), 6.87 - 6.84 (1H, m), 6.59 - 6.51 (2H, m) and 5.51 (2H, s).

IR vI"aX (DR)/crri 14043, 3461, 3312, 3198, 2970, 2748, 2438, 1923, 1650, 1514, 1497 and 1324; NMR 8H (400 MHz, DMSO) 7.9 (1H, d, J 3.5 Hz), 7.31 (2H,br 150 C 37 s), 6.97 (1H, t, J 8.0 Hz), 6.53 (1H, d, J 3.5 Hz), 6.45 (1H, dd, J 1.5, 8.0 Hz), 6.40 (1H, d, J7.5 Hz), 6.34 (1H, t, J 1.7 Hz), 5.48 (2H, s), 5.12 (2H, s), 2.80 (2H, q, J 7.5 Hz) and 1.27 (3H, t, J 7.5 Hz).

mp 251.2 - 251.5 C; IR v",aX (DR)/cni 13449, 3365, 3314, 3196, 2954, 2742, 1731, 1642, 1598, 1556, 1463 and 1407; NMR 8H (400 MHz, DMSO) 8.76 -151 C 48 8.72 (2H, m), 7.67 - 7.62 (3H, m), 7.36 (2H, br s), 6.97 (1H, t, J 8.0 Hz), 6.46 (1H, dd, J 1.5, 8.0 Hz), 6.43 (1H, d, J7.5 Hz), 6.36 (1H, t, J 1.7 Hz), 5.52 (2H, s) and 5.13 (2H, s).

mp 298.9 - 299.0 C; IR v",aX (DR)lcrn 13422, 3321, 3105, 3942, 1601, 1351, 1219, 1019 and 762; NMR 8H (400 MHz, DMSO) 11.09 (1H, br s), 8.13 (1H, s), 152 AF g6 7.91 (1H, d, J 3.0 Hz), 7.51 (1H, d, J 8.5 Hz), 7.43 - 7.31 (3H, m), 7.28 (1H, s), 7.00 (1H, d, J 8.0 Hz), 6.89 - 6.83 (1H, m), 6.39 (1H, s) and 5.73 (2H, br s).

mp 226.8 - 227.4 C;1R v~X (DR)/crri 13475, 3320, 2739, 1645, 1506, 1223, 1008 and 778; NMR SH (400 MHz, DMSO) 11.14 (1H, br s), 8.14 - 8.10 (1H, m), 7.90 (1H, d, J 3.5 Hz), 7.50 (1H, s), 7.40 - 7.31 (4H, m), 7.09 (1H, dd, J 8.0, 1.5 Hz), 6.85 (1H, dd, J 3.5, 1.5 Hz), 6.43 - 6.38 (1H, m) and 5.70 (2H, s).

mp 295.3 - 295.5 C; 1R v"~X (DR)/crri 1 3215, 1610, 1005, 758, 650 and 565;

NMR 8H (400 MHz, DMSO) 11.36 (1H, br s), 8.15 -8.11 (1H; m), 7.91 (1H, d, J

154 AF 77 3.5 Hz), 7.51 (1H, d, J 8.0 Hz), 7.46 (1H, t, J
. 2.5 Hz), 7.43 (2H, br s), 6.92 (1H, t, J 7.5 Hz), 6.86 (1H, dd, J 3.5, 2.0 Hz), 6.71 (1H, d, J 7.0 Hz), 6.53 - 6.49 (1H, m) and 5.93 (2H, s).

mp 258.6 - 258.7 C; IR vt,,ax (Nujol)/crri 1 3386, 3206, 1646, 1607 and 1481;

NMR 8H (400 MHz, DMSO) 8.33 (1H, dd, J 9.0, 4.5 Hz), 8.15 (1H, s), 7.92 (1H, d, J 3.5 Hz), 7.55 - 7.47 (1H, m), 7.47 - 7.35 (2H, s), 6.93 - 6.85 (2H, m) and 6.03 (2H, s).

mp 274.2 - 274.3 C; IR v~X (Nujol)/cni 1 3482, 3305, 3197, 2963, 1606, 1499 and 1420; NMR ~H (400 MHz, DMSO) 8.12 (1H, s), 7.87 (1H, d, J 3.0 Hz), 7.37 156 AG 99 (2H, s), 6.86 - 6.77 (3H, rn), 5.55 (2H, s) and 3.79 (3H, s); Anal. Calcd for ClsHIZN6O2F2 ~ 0.5 HZO: C, 52.32; H, 3.57, N, 22.88.
Found: C, 52.62; H, 3.31;

N, 22.72.

mp 204.2 - 204.4 C; NMR 8H (400 MHz, DMSO) 1.41 (9H, s), 4.37, (2H, d, J

6.0 Hz), 5.72 (2H, s), 6.83 (1H, d, J 6.0 Hz), 6.85 - 6.88 (1H, d, J 7.5 Hz), 7.14 -157 B 24 7.22 (1H, m), 7.30 (2H, d, J 4.0 Hz), 7.36 (2H, s), 7.48 (1H, t, J 6.0 Hz), 7.91 (1H, d, J 3.5 Hz), 8.12 - 8.14 (1H, m). Anal. Calcd for CZ1H23N7~3 C, 59.85; H, 5.50; N, 23.25. Found: C, 59.69; H, 5.54; N, 22.74.

mp >300 C dec; IR v~X (DR)/crri 13212, 1607, 1438, 1212, 1029 and 770;

158 AZ NMR SH (400 MHz, DMSO) 15.74 (1H, br s), 8.13 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.80 (2H, br s), 7.54 - 7.30 (3H, s), 6.86 (1H, dd, J 4.0, 2.0 Hz) and 5.85 (2H, s).

Mp 235.9 - 237.8 C; NMR ~H (400 MHz, DMSO) 8.15 -8.13 (1H, m), 7.93 -7.91 (1H, d, J 3.5 Hz), 7.84 - 7.82 (1H, d, J 2.5 Hz), 7.80 - 7.76 (1H, dd, J 2.5, 8.5 Hz), 7.43 - 7.37 (2H, s) 7.04 - 7.00 (1H, d, J 8.5 Hz), 6.89 - 6.86 (1H, dd, J

2.0, 3.5Hz), 5.71 - 5.69 (2H s), and 3.99 - 3.97 (3H s).

mp 277.4 - 277.9 C; NMR 8H (400 MHz, DMSO) 9.93 (1H, s), 8.15 - 8.12 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.55 (1H, d, J 8.0 Hz), 7.38 (2H, s), 7.34 (1H, s), 7.27 (1H, t, J 8.0 Hz), 6.96 (1H, d, J 7.5 Hz), 6.88 -6.85 (1H, m), 5.63 (2H, s) and 1.99 (3H, s).

mp >250 C dec; IR v"~X (DR)/ciri' 3035, 1968, 1654, 1464, 1354, 1247, 1032 and 746; NMR 8H (400 MHz, DMSO) 4.39 (2H, q, J 5.5 Hz),.5.81 (2H, s), 6.84 -6'89 (1H, m), 7.13 (1H, d, J 7.5 Hz), 7.31- 7.46 (3H, m), 7.55 (1H, d, J 7.5 Hz), 161 I~ 100 7.90 (1H, d, J 3.5 Hz), 8.12 - 8.16 (1H, m), 8.44 (3H, s). Anal. Calcd for ClsHisN~O - 2 HCl ~ 1.5 H20: C, 45.62; H, 4.79; N, 23.27. Found: C, 45.63; H, 4.71; N, 23.14.

mp 195.1- 195.2 C; IR v~X (DR)/crri' 3490, 3375, 3310, 3199, 2895, 1734, 1609, 1507, 1421, 1228, 1026, 1001 and 760; NMR 8H
(400 MHz, DMSO) 2.86 162 B 14 (6H, s), 5.58 (2H, s), 6.48 (1H, d, J 7.5 Hz), 6.64 (1H, dd, J 8.0, 2.0 Hz), 6.72 -6.75 (1H, rn), 6.84-6.87 (1H, m), 7.12 (1H, t, J7.5 Hz), 7.35 (2H, s), 7.90 (1H, d, J 3.5 Hz) and 8.10 - 8.14 (1H, m).

IR v~X (DR)lcrri 13489, 3324, 3199, 2560, 1605, 1235, 1121, 1048 and 762;

NMR 8H (400 MHz, DMSO) 8.12 (1H, d, J 2.5 Hz), 7.90 (1H, d, J 3.5 Hz), 7.44 -7.32 (4H, m), 7.16 (2H, d, J 9.0 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz) and 5.67 (2H, s).

mp 120.1- 121.0 C; IR v",aX (DR)lcrri 13318, 1772, 1709, 1607, 1462, 1395;

NMR 8H (400 MHz, DMSO) 8.15 - 8.14 (1H, m), 7.81 (1H, d, J 3.5 Hz), 7.77 (1H, t, J 8.0 Hz), 7.71 - 7.65 (4H, m), 7.33 (1H, d, J 8.0 Hz), 7.21 (2H, br s), 7.12 (1H, d, J 8.0 Hz), 6.88 (1H, dd, J 1.5, 3.5 Hz), 5.68 (2H, s), 4.80 (2H, s).

mp 259.7 - 259.8 C; IR v",ax (DR)/crri 1 3457, 3315, 3183, 2959, 2747, 1734, 1653, 1608, 1518, 1441, 1420 and 1386; NMR 8H (400 MHz, DMSO) 8.12 (1H, 165 C 60 d, J 1.0 Hz), 7.90 (1H, d, J 3.5 Hz), 7.35 (2H, br s), 6.93 (1H, dd, J 8.0, 11.5 Hz), 6.86 (1H, dd, 1.5, J 3.5 Hz), 6.58 (1H, dd, J 2.0, J 8.5 Hz) 6.47 - 6.39 (1H, m) , 5.49 (2H, s) and 5.19 ( 2H, s).

mp 210.3 - 211.2 C; NMR ~H (400 MHz, DMSO) 8.15 - 8.10 (1H, m), 7.89 (1H, d, J4.5 Hz), 7.35 (2H, br s), 7.18 (1H, s), 7.08 (1H, d, J 8.0 Hz), 6.85 (1H, dd, J

3.5, 1.5 Hz), 6.72 (1H, d, J 8.0 Hz), 5.55 (1H, s), 4.49 (2H, t, J 8.5 Hz) and 3.13 (2H, t, J 8.5 Hz).

IR v~X (Nujol)lcW 1 3486, 3319, and 1606; NMR 8n (400 MHz, DMSO) 8.15 -8.10 (1H, m), 7.92 - 7.87 (1H, d, J 3.5 Hz), 7.64 - 7.56 (1H, m), 7.54 - 7.47 (1H, 167 B 11 m), 7.46 - 7.35 (2H, s), 7.32 - 7.22 (1H, t, J 9.5 Hz), 6.88 - 6.84 (1H, dd, J 2.0, 3.5Hz), and 5.71 - 5.65 (2H s); Anal. Calcd for C15H1oN60FBr ~ 0.5 H20 : C, 45.25; H, 2.78; N, 21.11. Found: C, 45.10; H, 2.48;
N, 20.69.

Mp 204.0 - 204.2 C; IR v",aX (Nujol)lcrri' 3343 and 3208; NMR 8H (400 MHz, DMSO) 8.14 - 8.12 (1H, m), 7.91- 7.89(1H, dd, J
1.0, 3.5 Hz), 7.62 - 7.53(1H, m), 7.45 - 7.37 (2H, s), 7.05 - 6.97(1H, m), 6.88 - 6.85 (1H, dd, J 2.0, 3.5 Hz), and 5.76 - 5.74 (2H, s).

IR v~X (Nujol)/cW 13490 and 3321; NMR SH (400 MHz, DMSO) 8.15 - 8.13 (1H, m), 7.91 - 7.89 (1H, d, J 3.5 Hz), 7.78 - 7.72 (1H, m), 7.67 - 7.63 (1H, dd, J

2.0, 7.0 Hz), 7.46 - 7.38 (2H, s), 7.15 - 7.08 (1H, dd, J 9.0, 10.0 Hz) 6.88 - 6.85 (1H, dd, J 2.0, 3.5 Hz), and 5.67 - 5.64 (2H, s).

1R v~X (Nujol)/crri 13495 and 3304; NMR 8H (400 MHz, DMSO) 8.14 - 8.12 (1H, m), 7.90 - 7.88 (1H, dd, J 1.0, 3.5 Hz), 7.64 - 7.62 (1H, dd, J 1.0, 2.0 Hz), 170 B 1g 7.43 - 7.37 (2H, s), 6.87 - 6.84 (1H, dd, J 1.5, 3.5 Hz), 6.51 - 6.48 (1H, dd, J 1.0, 3.5 Hz), 6.46 - 6.44 (1H, dd, J 2.0, 3.5 Hz) and 5.67 - 5.65 (2H, s).

mp 219.3 C; IR v~X (Nujol)/ciri 13508, 3421, 3307, 3190, 2949, 1609 and 1506;

~ SH (400 MHz, DMSO) 8.14 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.43 (2H, s), 6.92 - 6.85 (2H, m), 6.72 ( 1H, dd, J 8.5, 5.0 Hz), 6.52 ( 1H, dd, J 9.5, 3.0 Hz), 5.47 (2H, s) and 5.19 (2H, s).

IR v~X (Nujol)/crri' 3490, 3304, 3182, 2986, 1779, 1762, 1603, 1345 and 1231;

~ ~H (400 MHz, DMSO) 8.16 (1H, d, J 8.5 Hz), 8.15 - 8.13 (1H, m), 7.92 172 B 1g (1H, d, J 3.5 Hz), 7.46 (1H, d, J 2.0 Hz), 7.45 - 7.36 (2H, s), 7.32 (1H, dd, J 8.5, 1.5 Hz), 6.88 - 6.86 (1H, m), 5.84 (2H, s) and 1.47 (9H, s).

mp 239.6 - 239.8 C; IR v~X (Nujol)/cni' 3323, 2936, 2733, 1772, 1734, 1609, 1508 and 1282; NMR 8H (400 MHz, DMSO) 9.07 (1H, s), 8.13 - 8.11 (1H, m), 7.89 (1H, d, J 3.5 Hz), 7.34 (2H, s), 6.87 - 6.84 (1H, m), 6.59 - 6.50 (3H, m), 5.41 (2H, s) and 4.57 (2H, s).

mp >200 C dcc; IR v~X (DR)/crri 1 3144, 2570, 2004, 1654, 1458, 1369, 1280, 1037 and 760; NMR SH (400 MHz, DMSO) 7.87 (1H, d, J 3.5 Hz), 7.13 (1H, d, J

11.5 Hz), 7.05 - 6.91 (2H, m), 6.51 (1H, dd, J 3.5, 1.0 Hz), 5.55 (2H, s) and 2.45 (3H, s).

mp 279.3 - 281.3 C; IR v",ax (DR)/crri 13462, 3202, 2952, 1653, 1510, 1462, 1416, 1342, 1293 and 1261; NMR 8H (400 MHz, DMSO)13.52 ( 1H, br s), 7.97 (1H, br s), 7.31 (1H, s), 7.25 (2H, br s), 6.96 (1H, t, J 7.5 Hz), 6.46 (1H, dd, J

1.0, 8.0 Hz), 6.42 (1H, d, J 7.0), 6.34 ( 1H, s), 5.50 ( 2H,s) and 5.13 (2H, s).

1R v~X (Nujol)/crri 13651, 3488, 3317, 1637, 1507 and 1331; NMR SH (400 MHz, DMSO) 11.04 (1H, s), 8.15 - 8.13 (1H, m), 7.92 (1H, dd, J 3.5, 1.0 Hz), 176 K 51 7.87 (1H, d, J 8.5 Hz), 7.41 (2H, s), 6.88 - 6.86 (1H, m), 6.85 -6.81 (2H, m) and 5.72 (2H, s); Anal. Calcd for C15H11N~04 ~ 1.0 H2O:
C, 48.52; H, 3.53, N, 26.24.

Found: C, 48.68; H, 3.20; N, 26.24.

mp 245.9 - 247.0 C; IR v,~X (DR)/crxi 13284, 3194, 1654, 1609, 1523; NMR 8H

(400 MHz, DMSO) 8.41 (1H, t, J 6.0 Hz), 8.14 - 8.13 (1H, m), 7.92 (1H, dd, J

1.0, 3.5 Hz), 7.73 (1H, t, J 7.5 Hz), 7.37 (2H, br s), 7.21 (1H, d, J 7.5 Hz), 6.93 (1H, d, J 7.5 Hz), 6.88 - 6.86 (1H, m), 5.74 (2H, s), 4.28 (2H, d, J 6.0 Hz), 1.88 (3H, s); Anal. Calcd for C1~H16N802 ~ 0.5 HZO ~ 0.1 C3H~N0: C, 54.58; H, 4.69, N, 29.80. Found: C, 54.90; H, 4.43; N, 29.46.

mp 216.7 - 218.4 C; IR v~X (DR)/cxri 13854, 3143, 2569, 2004, 1654, 1518, 1437, 1279, 1207, 1037 and 868; NMR 8H (400 MHz, DMSO) 1.90 (3H, s), 4.48 (2H, d, J 6.0 Hz), 5.73 (2H, s), 6.82 - 6.89 (2H, m), 7.15 - 7.23 (1H, m), 7.25 -7.46 (4H, m), 7.91 (1H, d, J 3.5 Hz), 8.12 - 8.15 (1H, m), 8.39 (1H, t, J 5.5 Hz).

Mp 215.8 - 216.9 C; IR v~X (Nujol)/cxri 13482 and 3305; NMR 8H (400 MHz, DMSO)8.13-8.11(lH,m),7.91-7.89(lH,d,J3.5Hz),7.55-7.52(lH,dd,J

179 B 11 3.0, 5.0 Hz), 7.42 - 7.40 (1H, m), 7.39 - 7.34 (2H, s), 7.11 - 7.08 (1H, dd, J 1.5, 5.0 Hz), 6.87 - 6.85 (1H, dd J 1.5, 3.5 Hz) and 5.66 - 5.64 (2H, s); Anal. Calcd for C13H1oN60S: C, 52.34; H, 3.38, N, 28.16. Found:
C, 52.53; H, 3.57; N, 28.22.

mp 278.4 - 279.9 C; IR vt"ax (DR)/crri 1 3468, 3184, 2967, 1735, 1604, 1436, 1322, 1234 and 1204; NMR 8n (400 MHz, DMSO) 7.87 (1H, d, J 3.0 Hz), 7.30 180 C 25 (2H, br s), 6.80 (1H, t, J 8.0 Hz), 6.58 (1H, dd, J 1.0, 8.0 Hz), 6.51 (1H, dd, J 3.0, 1.0 Hz), 6.11 (1H, d, J 7.0 Hz), 5.54 (2H, s), 4.93 (2H, br s), 2.45 (3H, s) and 2.1 (3H, s).

mp 210.3 - 211.2 C; NMR ~H (400 MHz, DMSO) 8.15 - 8.10 (1H, m), 7.89 (1H, IR v~X (Nujol)/crri 13501 and 3316; NMR 8H (400 MHz, DMSO) 8.13 - 8.11 (1H, m), 7.90 - 7.87 (1H, dd, J 1.0, 3.5 Hz), 7.43 - 7.32 (2H, s), 7.40 - 7.37 (1H, d, J 5.0 Hz), 6.90 - 6.87 (1H, d, J 5.0 biz), 6.86 - 6.84 (1H, dd, J 2.0, 3.5 Hz), 5.73 - 5.72 (2H, s), and 2.37 - 2.35 (3H, s).

mp 92.3 - 92.7 C; 1R v",ax (DR)/cni 1 3124, 3073, 2926, 1609, 1520, 1411; NMR

8u (400 MHz, DMSO) 8.18 - 8.17 (1H, m), 7.93 (1H, d, J 3.0 Hz), 7.80 (1H, t, J

A 7'S Hz), 7.37 (1H, d, J7.5 Hz), 7.19 (1H, d, J7.5 Hz), 6.87 (1H, dd, J 1.5; 3.5 M Hz), 5.94 - 5.75 (3H, m), 5.78 (2H, s), 5.28 - 5.07 (6H, m), 4.48 (2H, s), 4.43 -4.12 (4H, m), 4.02 - 3.99 (2H, m); Anal. Calcd for C~HZSN~O2: C, 65.00; H, 5.68, N, 22.10. Found: C, 65.23; H, 5.80; N, 21.60.

mp 152.0 -153.5 C; IR v",aX (DR)/cni 13515, 3300, 3183, 2934, 2822, 1631, 1450, 1434; NMR 8H (400 MHz, DMSO) 7.89 (1H, d, J 3.0 Hz), 7.79 (1H, t, J

183 B 27 7.5 Hz), 7.33 (2H, br s), 7.34 (1H, d, J 7.5 Hz), 7.02 (1H, d, J 7.5 Hz), 6.53 - 6.51 (1H, m), 5.74 (2H, s), 4.43 (2H, s), 2.46 (3H, s), 3.33 (3H, s); Anal. Calcd for C1~H1~N~02 : C, 58.11; H, 4.88, N, 27.89. Found:
C, 57.75; H, 4.85; N, 27.59.

mp 219.7 - 220.4 C IR v~X (DR)/ciri 13450, 3312, 2920, 2728, 1737, 1638, 1438, 1354, 1326, 1291and 1234; NMR 8H (400 MHz, DMSO) 7.85 (1H, d, J 3.0 Hz), 7.30 (2H, br s), 7.01 (2H, d, J 8.5 Hz), 6.52 - 6.47 (3H, m), 5.41 (2H, s), 5.12 (2H, s) and 2.44 (3H, s).

mp 155.6 -157.1 C; IR v~X (DR)/ciri 1 3332, 3197, 2857, 1655, 1605, 1525, 1420; NMR 8n (400 MHz, DMSO) 8.14 - 8.13 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.79 (1H, t, J7.5 Hz), 7.37 (1H, d, J 7.5 Hz), 7.36 (2H, br s), 7.05 (1H, d, J 7.5 Hz), 6.88 - 6.86 (1H, m), 5.98 - 5.86 (1H, m), 5.76 (2H, s), 5.29 - 5.24 (1H, m), 5.17 - 5.13 (1H, m), 4.48 (2H, s), 4.06 - 4.00 (2H, m); Anal. Calcd for C18H1~N~02: C, 59.50; H, 4.72, N, 26.97. Found:
C, 59.39; H, 4.70; N, 26.99.

mp 149.0 - 149.3 C; IR v",ax (DR)lc~i 13514, 3295, 3168, 2861, 1634, 1502, 1435; NMR ~H (400 MHz, DMSO) 7.88 (1H, d, J 3.5 Hz), 7.79 (1H, t, J 7.5 Hz), 7.37 ( 1H, d, J 7.5 Hz), 7.33 (2H, br s), 7.04 ( 1H, d, J 7.5 Hz), 6.52 - 6.51 ( 1H, m), 5.96 - 5.86 (1H, m), 5.74 (2H, s), 5.30 - 5.24 (1H, m), 5.17 - 5.13 (1H, m), 4.49 (2H, s), 4.06 - 4.00 (2H, m), 2.46 (3H, s);
Anal. Calcd for C19H19N7C2 ~ 0.2 H20: C, 59.90; H, 5.13, N, 25.73. Found: C, 59.71;
H, 5.02; N, 25.64.

mp 191.7 -191.9 C; IR v",aX (Nujol)/crri 13501, 3307, 3189, 2974, 1611, 1527 and 1338; NMR 8H (400 MHz, DMSO) 8.12 - 8.15 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.76 (1H, d, J 8.5 Hz), 7.67 (1H, d, J 2.0 Hz), 7.44 - 7.36 (2H, s), 7.16 (1H, dd, J 8.5, 2.0 Hz), 6.87 - 6.85 (1H, m), 5.78 (2H, s), 3.22 (1H, quin, J 6.5 H,z) and 1.22 (6H, d, J 6.5 Hz).

mp 228.9 - 229.9 C; IR v~X (DR)/crri' 3461, 3317, 3195, 1606, 1504, 1320, 1026 and 818; NMR 8H (400 MHz, DMSO) 8.16-8.14 (1H, m), 7.98 (1H, d, J 8.0 188 B 32 ~), 7.94 (1H, d, J 3.5, 1.0 Hz), 7.91 (1H, d, J 8.0 Hz), 7.78 - 7.73 (1H, m), 7.64 - 7.58 (1H, m), 7.36 (1H, d; J 8.5 Hz), 7.36 (2H, br s), 6.88 (1H, dd, J 3.5, 1.5 Hz) and 5.98 (2H, s).

NMR 8H (400 MHz, DMSO) 8.14 - 8.12 (1H, m), 7.92 - 7.89 (1H, dd, J 1.0, 3.5 189 K 23 Hz), 7.35 - 7.31 (2H, d, J 8.5 Hz), 7.28 - 7.16 (2H, s), 6.88 - 6.85 (1H, dd, J 1.5, 3.5 Hz), 5.66 - 5.64 (2H, s), and 2.82 - 2.80 (3H, s); M/Z 322 (M+H)+.

mp 290.2 - 290.3 C; IR v~X (DR)lcmi 13491, 3338, 3205, 3128, 2936, 1710, 1616, 1490, 1458; NMR 8H (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.93 (1H, t, J 7.5 Hz), 7.90 (1H, dd, J 1.0, 3.5 Hz), 7.84 (1H, d, J 7.5 Hz), 7.56 (1H, d, J 7.5 Hz), 7.34 (2H, br s), 6.86 (1H, dd, J 2.0, 3.5 Hz), 6.69 (1H, q, J 7.5 Hz), 2.48 (3H, s), 1.98 (3H, d, J 7.5 Hz); Anal. Calcd for C17H15N~02: C, 58.45; H, 4.33, N, 28.05. Found: C, 58.26; H, 4.42; N, 27.67.

mp 186.1 - 189.1 C; IR v",aX (DR)/crri 13458, 1598, 1509, 1460, 1329, 1267 and 1220; NMR 8H (400 MHz, DMSO) 11.73 (1H, s), 7.59 (1H, s), 7.17 (1H, s), 6.97 191 C 16 (1H, t, J 7.8 Hz), 6.95 - 6.83 (2H, br s), 6.45 (1H, dd, J 1.5, J 8.0 Hz ), 6.40 (1H, d, J 8.0 Hz), 6.38 - 6.31 (1H, m), 5.47 (2H, s) and 5.13 (2H,s).

NMR 8H (400 MHz, CD30D) 8.84 (1H, d, J4.5 Hz), 8.77 (1H, d, J 8.0 Hz), 8.33 (1H, t, J 1.7 Hz), 8.2 (1H, dd, J 2.0, 8.0 Hz), 8.06 (1H, td, J 7.8, 2.0 Hz), 7.81 192 ~ 2 ( 1H, d, J 7.5 Hz), 7.65 - 7.58 (2H, m) and 5.88 (2H, s); M/Z 349 (M+H)+;

Retention time 1.77 min.

mp 253.5 - 254.0 C; IR v~X (DR)/crri l 3320, 1611, 1414, 1315, 1255, 1026 and 767; NMR 8H (400 MHz, DMSO) 2.01 (3H, s), 5.59 (2H, s), 6.84 - 6.88 (1H, m), 7.22 (2H, d, J 8.5 Hz), 7.36 (2H, s), 7.54 (2H, d, J 8.5 Hz) 7.90 (1H, d, J 3.5 Hz), 8.11-8.14(lH,m),9.97(lH,s).

mp 136.5 -137.6 C; IR v~X (Nujol)/crri 13489, 3311, 3195, 2954, 1774 and 1613; NMR 8H (400 MHz, DMSO) 8.24 (1H, s), 8.04 (1H, d, J2.0 Hz), 8.00 194 B 36 (1H, d, J 3.5 Hz), 7.96 (1H, dd, J 8.5, 2:0 Hz), 7.52 - 7.44 (2H, s), 7.40 (1H, d, J

8.5 Hz), 6.99 - 6.95 (1H, m), 5.83 (2H, s), 5.54 (2H, s), 3.66 (2H, t, J 8.0 Hz), 0.93 (2H, t, J 8.0 Hz) and 0.00 (9H, s); Anal. Calcd for CZIH2sN~OSSi ~ 0.1 H20:

C, 51.97; H, 5.23, N, 20.20. Found: C, 51.97; H, 5.19; N, 19.86.

IR v"~X (Nujol)/crri' 3652, 3506, 3307, 3196, 2990, 2878, 1633, 1521 and 1344;

NMR 8H (400 MHz, DMSO) 8.14 (1H, s), 7.94 - 7.88 (2H, m), 7.46 (1H, s), 7.40 195 B 12 (2H, s), 7.23 (1H, dd, J 8.5, 2.0 Hz), 6.88 - 6.85 (1H, m), 5.78 (2H, s), 2.80 (2H, q, 7.5 Hz) and 1.17 (3H, t, J 7.5 Hz); Anal. Calcd for C1~H15N~03 ~ 0.25 H20: C, 55.21; H, 4.22, N, 26.51. Found: C, 55.47; H, 4.12;
N, 26.25.

mp 178.4-179.0 C; IR v",aX (Nujol)/crri 13469 and 3311; NMR &H (400 MHz, DMSO) 8.13 - 8.11 (1H, m), 7.90 - 7.88 (1H, dd, J 1.0, 3.5 Hz), 7.37 - 7.32 (2H, s), 7.32 - 7.29 (1H, dd, J 1.5, 5.5 Hz), 6.92 -6.89 (1H, dd, J 3.5, 5.5 Hz), 6.87 -6.84 (2H, m), 4.70 - 4.64 (2H, t, J 7.0 Hz), and 3.53 - 3.48 (2H, t, J 7.0 Hz);

Anal. Calcd for C14H12N6OS; C, 53.84; H, 3.87; N, 26.89. Found: C, 53.98; H, 3.87; N, 26.50.

mp 188.3 - 188.5 C; IR vI"aX (DR)/cni 13324, 3189, 2964, 1649, 1513; NMR bH

(400 MHz, DMSO) 8.14 - 8.13 (1H, m), 7.93 (1H, d, J 3.5 Hz), 7.67 (1H, t, J 7.5 Hz), 7.34 (2H, br s), 7.20 (1H, d, J 7.5 Hz), 6.89 (1H, d, J7.5 Hz), 6.87 - 6.86 (1H, m), 5.75 (2H, s), 2.93 (1H, sept, J 7.0 Hz), 1.12 (6H, d; J 7.0 Hz); Anal.

Calcd for C1~H1~N~0: C, 60.88; H, 5.11, N, 29.22.
Found: C, 61.03; H, 5.13; N, 28.95.

IR v~x (DR)/cni 13466, 3312, 3187, 2958, 2850, 1639, 1511, 1221, 1047, 756 and 599; NMR 8H (400 MHz, DMSO) 8.13 (1H, s), 8.09 (1H, s), 7.91 (1H, d, J

3~0 ~)' 7.72 (1H, d, J 8.5 Hz), 7:68 (1H, s), 7.42 (1H, d, J 8.5 Hz), 7.37 (2H, br s), 6.88 - 6.83 (1H, m), 5.82 (1H, d, J 9.5 Hz), 5.77 (2H, s), 3.90 - 3.80 (1H, m), 3.77 - 3.64 (1H, m), 2.45 - 2.30 (1H, m), 2.10 -1.88 (2H, m), 1.80 - 1.63 (1H, m), 1.62 -1.49 (2H, m).

mp 226.5 - 227.9 C; IR vI"aX (DR)/crri l 3466, 3316, 3182, 2962, 1645, 1606, 1546, 1514, 1473; NMR $H (400 MHz, DMSO) 8.14 -8.13 (1H, m), 7.92 (1H, d, 199 B 7 J 3.0 Hz), 7.33 (2H, br s), 7.07 - 7.06 (1H, m), 6.88 - 6.86 (2H, m), 5.71 (2H, s), 2.88 (1H, sept, J 7.0 Hz), 2.82 (1H, sept, J 7.0 Hz), 1.14 (6H, d, J 7.0 Hz), 1.09 (6H, d, J 7.0 Hz).

mp > 300 C dec; IR v~X (DR)/ciri 13100, 1662, 1465, 1281, 1032, 782 and 592;

NMR 8H (400 MHz, DMSO) 8.16 - 8.13 (1H, m), 8.07 (1H, s), 7.92 (1H, d, J 3.5 Hz), 7.68 (1H, s), 7.54 (1H, d, J 8.5 Hz), 7.35 (1H, dd, 8.5, 1.5 Hz), 6.87 (1H, dd, J 3.5, 2.0 Hz) and 5.76 (1H, s) IR v",aX (Nujol)/cni 12999, 1656, 1530 and 1461;
NMR 8H (400 MHz, DMSO) 11.10(lH,s),8.14(lH,d,JI.OHz),7.92(lH, d,J3.5Hz),7.72(lH,d,J2.5 Hz), 7.61 (1H, dd, J 8.5, 2.5 Hz), 7.0 (1H, d, J
8,5 Hz), 6.86 - 6.88 (1H, m), 5.67 (2H, s) and 5.11- 5.16 (3H, s).

mp 210.5 - 211.6 C; IR vt"aX (F1I,M)/crri 1 3352, 3204, 3001, 1659, 1569, 1510, 1440; NMR 8H (400 MHz, DMSO) 8.14 (1H, m), 7.93 (1H, d, J 3.5 Hz), 7.76 (1H, t, J 7.5Hz), 7.43 (1H, d, J 7.5 Hz), 7.36 (2H, br s), 7.03 (1H, d, J 7.5 Hz), 6.87 (1H, dd, J 2.0, 3.5 Hz), 6.75 (1H, dd, J 10.5, 17.5 Hz), 6.09 (1H, dd, J 2.0, 17.5 Hz), 5.78 (2H, s), 5.43 (1H, dd, J 1.5, 10.5 Hz); Anal. Calcd for C16H13N~0:

C, 60.18; H, 4.10, N, 30.69. Found: C, 60.14; H, 4.20; N, 30.39.

IR v,i,aX (Nujol)/cni 13514, 3298 and 1761; NMR SH
(400 MHz, DMSO) 8.16 -203 AS 12 8.15 (1H, m), 7.89 - 7.86 (1H, dd, J 1.0, 3.5 Hz), 7.80 - 7.40 (2H, s), 6.89 - 6.86 (1H, dd, J 1.5, 3.5 Hz), and 1.66 - 1.64 (9H, s).

mp 143.6 - 144.5 C; IR v",aX (DR)lcni l 3644, 3315, 3195, 2978, 1743, 1608, 1163, 1086 and 746; NMR 8H (400 MHz, DMSO) 8.14 -8.10 (1H, m), 8.05 (1H, 204 B 16 d, J 8.0 Hz), 7.88 (1H, d, J 3.5 Hz), 7.81 (1H, s), 7.66 (1H, d, J7.5 Hz), 7.42 (2H, br s), 7.34 (1H, t, J 8.0 Hz), 7.23 (1H, t, J 8.0 Hz), 6.85 (1H, dd, J 3.5, 2.0 Hz), 5.78 (2H, s) and 1.63 (9H, s) IR v~x (DR)lcrri 13431, 3325, 3217, 1646, 1504, 1431;
NMR 8H (400 MHz, DMSO) 9.87 - 9.86 (1H, m), 8.14 (1H, m), 8.05 (1H, t, J 8.0 Hz), 7.94 - 7.92 205 B 19 (1H, m), 7.88 (1H, d, J 8.0 Hz), 7.52 (1H, d, J 8.0 Hz), 7.38 (2H, br s), 6.88 -6.87 (1H, m), 5.91 (2H, s); Anal. Calcd for C15H1N~02 ~ 0.3 H20: C, 55.15; H, 3.58, N, 30.01. Found: C, 55.33; H, 3.35; N, 29.64.

IR vi"aX (film)/cni 13327, 3209, 2987, 1730, 1664, 1390, 1168, 959, 745 and 664;

NMR ~H (400 MHz, DMSO) 8.16 (1H, s), 8.09 (1H, d, J 8.0 Hz), 7.97 - 7.92 206 B 30 (2H, m), 7.47 (1H, d, J 7.5 Hz), 7.44 - 7.35 (2H, br s), 7.31 (1H, t, J 7.5 Hz), 7.20 (1H, t, J 7.0 Hz), 6.89 (1H, dd, J 3.5, 1.5 Hz), 6.03 - 5.96 (3H, m) and 1.64 (9H, s) mp 289.1 - 289.3 C;1R v~X (DR)/crri 1 3442, 3317, 3189, 1649, 1607, 1519, 1332, 1118, 1023 and 763; NMR SH (400 MHz, DMSO) 11.21 (1H, br s), 8.13 207 AF 71 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.46 (1H, d, 8.0 Hz), 7.38 (2H, br s), 7.33 (1H, d, J 8.0 Hz), 7.06 (1H, t, J 8.0 Hz), 6.96 (1H, t, J
7.0 Hz), 6.86 (lH,.dd, J 3.5, 1.5 Hz), 6.31 (1H, s) and 5.79 (2H, s) NMR 8H (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.91 - 7.88 (1H, dd, J 1.5, 3.5 Hz), 7.46 - 7.36 (2H, s), 6.98 - 6.96 (1H, d, J 3.5 Hz), 6.87 - 6.84 (1H, dd, J 1.5, 3.5 Hz), 6.72 - 6.69 (1H, d, J 3.5 Hz), 5.76 - 5.74 (2H, s), 2.52 - 2.48 (2H, h, J

2.0, 3.5 Hz) and 1.20 -1.14 (3H, t, J 7.5 Hz); MlZ
327 (M+H)~.

mp >250 C dec; IR v~X (DR)/crri 13489, 3316, 2919, 1610, 1326, 1037, 862, 760 and 593; NMR 8H (400 MHz, DMSO) 8.13 - 8.11 (1H, m), 7.90 (1H, d, J 2.5 Hz), 7.38 (2H, br s), 6.92 (1H, d, J 2.0 Hz), 6.88 (1H, d, J 8.0 Hz), 6.86 (1H, dd, J 3.5, 2.0 Hz), 6.79 (1H, dd, J 8.0, 1.5 Hz), 6.00 (2H, s) and 5.56 (2H, s).

IR v~X (DR)/crri 13427, 3318, 3201, 2966, 1605, 1503, 1415, 1281, 1027 and 762; NMR 8H (400 MHz, DMSO) 1.08 (3H, t, J 7.0 Hz), 2.39 (2H, q, J 7.0 Hz), 210 C 36 4.91 (2H, s), 5.44 (2H, s), 6.54 (1H, d, J 8.0 Hz), 6.80 - 9.62 (2H, m), 6.97 (1H, s), 7.34 (2H, s), 7.89 (1H, s), 8.12 (1H, s). Anal.
Calcd for C1~H1~N~0 ~ 0.6 H20:

C, 58.98; H, 5.30; N, 28.32. Found: C, 59.37; H, 5.02; N, 28.05.

mp 257.1- 257.3 C; IR v",ax (DR)/cni 13491, 3343, 3205, 3131, 2971, 1973, 1691, 1626, 1499, 1437, 1239, 1030 and 764; NMR 8H
(400 MHz, DMSO) 6.26 (2H, s), 6.86 - 6.91 (1H, m), 7.33 (2H, s), 7.63 (2H, t, J 7.5 Hz), 7.77 (1H, t, J

7.5 Hz), 7.94 (1H, d, J 3.0 Hz), 8.11- 8.16 (3H, m).

IIZ ymaX (DR)/crri 13321, 1608, 1438 1304 1025 and 757 NMR bu (400 MHz DMSO) 5.67 (2H, s). 6.86 - 6.88 (1H, m) 7.05~1H d J 7.5 Hz) 7.20 (1H dd J

212 R 58 5~0 3.5 Hz), 7.35 (1H, t, J 8.0 Hz), 7.39 (2H s) 7.55 - 7.58 (1H m) 7.72 11H

d~ J 7.5 Hz), 7.85 (1H, dd, J 5.0, 1.0 Hz) 7.92 (1H
d. J 3.5 Hz) 7.98 (1H dd J

3.5, 1.0 Hz), 8.12 - 8.15 (1H, m), 10.24 (1H s).

IR v,I,aX (DR)/ctri 1 3285, 1975, 1625, 1461; NMR
8H (400 MHz, DMSO) 8.14 213'AU 29 (1H, m), 7.92 (1H, d, J 3.0 Hz), 7.80 (1H, t, J 7.5 Hz), 7.44 (1H, d, J 7.5 Hz), 6.98 (1H, d, J 7.5 Hz), 6.87 {1H, dd, J 1.5, 3.5 Hz), 5.75 (2H, s), 4.52 (2H, s).

IR v~,~ (DR)/cmi 13321, 2956, 1610, 1234, 1027and 757; NMR $H (400 MHz, DMSO) 0.99 (9H, s), 2.14 (2H, s), 5.63 (2H, s), 6.85 - 6.89 (1H, m), 6.94 (1H, d, J 8.0 Hz), 7.27 (1H, t, J 7.5 Hz), 7.33 - 7.45 (3H, m), 7.59 (1H, d, J 9.0 Hz), 7.92 (1H, d, J 3.5 Hz), 8.12 - 8.15 (1H, m).

IR vi,,aX (DR)/cni 13510, 3278, 1631, 1425, 1293, 1217, 1024 and 757; NMR 8H

(400 MHz, DMSO) 0.71- 0.79 (4H, m), 1.72 (1H, tt, J 5.5, 7.0 Hz), 5.63 (2H, s), 6.85 - 6.89 (1H, m), 6.96 (1H, d, J 8.0 Hz), 7.27 (1H, t, J 7.5 Hz), 7.32 - 7.45 (3H, m), 7.55 (1H, d, J 8.0 Hz), 7.92 (1H, dd, J
3.5, 1.0 Hz), 8.12 - 8.15 (1H, m), 10.19 (1H, s). Anal. Calcd for C19H17N702 ~ 0.15 HZO: C, 60.36; H, 4.61; N, 25.93. Found: C, 60.89; H, 4.62; N, 25.54.

mp 178.3 -178.5 C; ILZ v,~X (DR)/crri 13472, 3324, 3194, 2964, 1641, 1598, 1510; NMR 8K (400 MHz, DMSO) 8.14 (1H, m), 7.92 (1H, dd, J 1.0, 3.5 Hz), 7.66 (1H, t, J 8.0 Hz), 7.35 (2H, br s), 7.17 (1H, d, J 8.0 Hz), 6.90 (1H, d, J 8.0 Hz), 6.87 (1H, dd, J 2.0, 3.5 Hz), 5.73 (2H, s), 2.63 (2H, t, J 7.5 Hz), 1.59 (2H, sext, J 7.5 Hz), 0.83 (3H, t, J 7.5 Hz); Anal. Calcd for C1~H1~N~0 ~ 0.1 C4H$Oa:

C, 60.72; H, 5.21, N, 28.49. Found: C, 60.85; H, 5.22; N, 28.29.

mp 146.7 -149.3 C; IR v~X (DR)/cni 13518, 3323, 2955, 1605, 1511; NMR 8H

(400 MHz, DMSO) 8.14 - 8.13 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.79 (1H, t, J 7.5 Hz), 7.35 (2H, br s), 7.35 (1H, d, J 7.5 Hz), 7.05 (1H, d, J 7.5 Hz), 6.87 (1H, dd, J 1.5, 3.5 Hz), 5.75 (2H, s), 4.46 (2H, s), 3.22 (2H, d, J 6.5 Hz), 1.77 - 1.87 (1H, m), 0.85 (6H, d, J 6.5 Hz); Anal. Calcd for C19Ha1N~02 ~ 0.5 HzO: C, 58.75; H, 5.71, N, 25.24. Found: C, 58.87; H, 5.49; N, 24.92.

mp 196.0 - 196.1 C; IR v~,~ (DR)lcrri 13481, 3325, 3203, 1646, 1607, 1518, 1488; NMR 8n (400 MHz, DMSO) 8.14 (1H, m), 7.92 (1H, d, J 3.5 Hz), 7.80 (1H, t, J7.5 Hz), 7.50 (1H, d, J7.5 Hz), 7.38 (2H, br s), 7.04 (1H, d, J7.5 Hz), 6.87 (1H, dd, J 1.5, 3.5 Hz), 5.77 (2H, s), 4.64 (2H, s).

IR v~X (DR)/ciri' 3480, 3379, 3199, 2958, 2761, 2104, 1879, 1776, 1659, 1516, 1439, 1334, 1024, 762 and 575; NMR 8H (400 MHz, DMSO) 1.10 (6H, d, J 7.0 Hz), 2.92 (1H, sept, J 6.5 Hz), 4.93 (2H, s), 5.44 (2H, s), 6.54 (1H, d, J 8.0 Hz), 6.80 - 6.88 (2H, m), 7.09 (1H, d, J 2.0 Hz), 7.34 (2H, s), 7.88 (1H, d, J 3.5 Hz), 8.10 - 8.13 (1H, m). Anal. Calcd for Cl$HI9N~0 ~
0.3 H20: C, 60.93; H, 5.57; N, 27.63. Found: C, 60.77; H, 5.50; N, 27.42.

mp 223.3 - 223.4 C; NMR SH (400 MHz, DMSO) 8.14 (1H, m), 7.92 (1H, dd, J

220 AV 26 1.0, 3.5 Hz), 7.82 (1H, t, J7.5 Hz), 7.37 (1H, d, J7.5 Hz), 7.36 (2H, br s), 7.07 (1H, d, J7.5 Hz), 6.87 (1H, dd, J 1.5, 3.5 Hz), 5.78 (2H, s), 4.18 (2H,, s).

NMR 8H (400 MHz, DMSO) 9.48 - 9.45 (1H, s), 8.12 - 8.10 (1H, m), 7.90 - 7.88 A (1H, dd, J 1.0, 3.5 Hz), 7.36 - 7.30 (2H, s), 7.17 - 7.12 (2H, dd, J 2.0, 8.5 Hz), W 6.86-6.84(lH,dd,J2.0,3.5Hz),6.74-6.70(2H,dd,J2.0,8.5Hz)and5:53-5.51 (2H, s); M/Z 309 (M+H)*.

IR v",ax (DR)/crri' 3483, 3319, 3200, 2961, 1953, 1709, 1612, 1439, 1343, 1220, 995 and 761; NMR ~H (400 MHz, DMSO) 6.37 (2H, s), 6.86 - 6.91 (1H, m), 222 B 18 7.35 (2H, s), 7.94 (1H, d, J 3.0 Hz), 8.15 (1H, s), 8.37 (2H, d, J 8.5 Hz), 8.43 (2H, d, J 8.5 Hz). Anal. Calcd for Cl6HnN~0a ~ 0.2 H20: C, 52.09; H, 3.11; N, 26.58. Found: C, 51.94; H, 3.05; N, 26.27.

IR v"~X (DR)/ciri 14013, 3601, 3456, 3209, 2959, 2237, 1938, 1708, 1625, 1505, 1171, 1002, 827 and 733; NMR 8H (400 MHz, DMSO) 6.33 (2H, s), 6.84 - 6.91 223 B 41 (1H, m), 7.34 (2H, s), 7.94 (1H, d, J 3.5 Hz), 8.09 - 8.18 (3H, m), 8.28 (2H, d, J

8.0 Hz). Anal. Calcd for C1~H11N~02 ~ 0.7 H20: C, 57.05; H, 3.49; N, 27.39.

Found: C, 56.97; H, 3.12; N, 27.37.

IR v~x (DR)/czri 13423, 3321, 3212, 1641, 1511, 1420, 1316, 1136 and 780;

NMR 8H (400 MHz, DMSO) 0.87 (3H, t, J 7.5 Hz), 1.54 -1.66 (2H, m), 2.96 -3.04 (2H, m), 5.65 (2H, s), 6.85 - 6.88 (1H, m), 7.00 - 7.03 (2H, m), 7.10 - 7.16 (1H, m), 7.30 (1H, t, J 7.5~Hz), 7.36 (2H, s), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.12 -8.15 (1H, m), 9.79 (1H, s). Anal. Calcd for C18H19N~03S:
C, 52.29; H, 4.63; N, 23.70. Found: C, 52.22; H, 4.70; N, 23.36.

IR v",aX (DR)/crri 13477, 3319, 3114, 1609, 1479, 1414, 1349, 1162, 956 and 763;

NMR SH (400 MHz, DMSO) 5.63 (2H, s), 5.85 - 6.89 (1H, m), 6.92 (1H, t, J 1.5 Hz), 7.02 - 7.11 (3H, m), 7.26 - 7.33 (2H, m), 7.37 (2H, s), 7.93 (1H, dd, J 3.5, 1.0 Hz), 8.12- 8.15 (1H, m), 10.62 (1H, s).

mp 221.4 - 221.5 C; IR vex (DR)/cxri l 3569, 3134, 2701, 2421, 1656, 1460;

NMR 8H (400 MHz, DMSO) 8.14 (1H, m), 7.92 (lH,.dd, J 1.0, 3.5 Hz), 7.88 (1H, t, J 7.5 Hz), 7.48 (1H, d, J7.5 Hz), 7.16 (1H, d, J7.5 Hz), 6.88 - 6.87(1H, m), 5.80 (2H, s), 4.27 - 4.24 (2H, m), 2.60 - 2.56 (3H, m).

IR y"LX (DR)/cxri 14011, 3491. 3377, 3210, 3125, 2975, 2663, 2106, 1924, 1740, 1618, 1438, 1201, 1004, 796 and 752: NMR 8x; (400 MHz, DMSO) 1.14 (6H, t, J

227 B 24 6.5 Hz), 3.46 (4H, g, J 6.5 Hz), 6.00 (2H, s), 6.76 (2H, d, J 9.0 Hz), 6.87 (1H, s), 7.26 (2H, s), 7.85 - 7.97 (3H, m), 8.13 f 1H, s).
Anal. Calcd for CaoH IN~Oa. ~ 0.6 H20: C, 59.72: H, 5.56: N, 24.38. Found: C, 60.00:
H, 5.40; N 24.03.

mp 164.3 -169.3 C; IR v~X (DR)/ciri 13376, 3199, 2964; 1659, 1613, 1516, 1441; NMR 8H (400 MHz, DMSO) 8.53 (1H, d, J 2.0 Hz), 8.12 - 8.11 (1H, m), 7.89 (1H, d, J 3.5 Hz), 7.62 (1H, dd, J 2.5, 8.0 Hz), 7.35(2H, br s), 7.26 (1H, d, J

7.5 Hz), 6.85 (1H, dd, J 1.5, 3.5 Hz), 5.67 (2H, s), 2.99 (1H, sept, J 7.0 Hz), 1.20 (6H, d, J 7.0 Hz); Anal. Calcd for C1~H1~N~0 ~ 0.5 H20: C, 59.29; H, 5.27, N, 28.47. Found: C, 59.28; H, 5.16; N, 28.23.

mp'258.2 - 258.4 C; IR v~X (DR)/cW ' 3367, 3200, 2932, 1671, 1243, 1178, 1033, 797 and 610; NMR bH (400 MHz, DMSO) 8.12 -8.07 (3H, m), 7.91 (1H, d, J 3.5 Hz), 7.15 - 7.09 (4H, m), 6.85 (1H, dd, J 3.5, 1.5 Hz), 6.I0 (2H, s) and 3.89 (3H, s).

IR v~X (DR)/cni 13436, 3320, 3208, 2977, 1609, 1370, 1323, 1155, 1025, 840 and 768; NMR 8H (400 MHz, DMSO) 8.12 - 8.10 (1H, m), 7.89 (1H, d, J 3.5 Hz), 7.78 (1H, d, J 4.0 Hz), 7.73 (1H, d, J 2.5 Hz), 7.33 (2H, br s), 6.88 - 6.84 (2H, m), 6.76 (1H, d, J4.0 Hz), 6.07 (2H, s) and 1.50 (9H, s).

mp 321.8 - 322.2 C; IEZ vt"aX (DR)/crri 13993, 3233, 1645, 1515, 1437, 1336, 1102, 854 and 759; NMR SH (400 MHz, DMSO) 11.56 (1H, br s), 8.13 - 8.11 231 AF 76 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.58 (1H, d, J
2.0 Hz), 7.55 (1H, t, J 3.5 Hz), 7.42 (2H, br s), 6.86 (1H, dd, J 3.5, 2.0 Hz), 6.73 (1H, d, J.2.0 Hz), 6.52 (1H, dd, J 3.0, 2.0 Hz) and 5.94 (2H, s).

IR v",aX (DR)lcrri 13216, 1713, 1610, 1505, 1421, 1185, 1124, 1026, 886 and 763;

NMR bH (400 MHz, DMSO) 2.13 (3H, s), 2.35 (3H, s), 5.62 (2H, s), 6.85 - 6.88 232 AX 20 (1H, m), 6.90 - 6.94 (1H, m), 6.98 - 7.03 (1H, m), 7.11 (1H, d, J 8.0 Hz), 7.30 (1H, t, J 7.5 Hz), 7.31 (2H, s), 7.91 (1H, d, J
3.5 Hz), 8.11- 8.14 (1H, m), 10.46 (1H, s).

mp 219.7 - 222.3 C; IR v,I,aX (DR)/crri' 3326, 3191, 2821, 2772, 1595, 1504, 1432; NMR FH (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.91 (1H, dd, J 1.0, 3.5 ~)' 7'74 (1H, t, J 7.5 Hz), 7.35 (1H, d, J 7.5 Hz), 7.31 (2H, br s), 6.98 (1H, d, J

7.5 Hz), 6.86 (1H, dd, J2.0, 3.5 Hz), 5.74 (2H, s), 3.46 (2H, s), 2.15 (6H, s);

Anal. Calcd for C1~H18N80: C, 58.28; H, 5.18, N, 31.97. Found: C, 57.94; H, 5.17; N, 31.70.

mp 168.3 -168.5 C; IR v"~x (DR)lcrti 13416, 3322, 3180, 2911, 1646, 1612, 1509, 1436; NMR 8H (400 MHz, DMSO) 8.13-8.12 (1H, m), 7.91 (1H, dd, J 1.0, 3.5 Hz), 7.74 (1H, t, J 7.5 Hz), 7.32 (1H, d, J
7.5 Hz), 7.31 (2H, br s), 7.02 (1H, d, J 7.5 Hz), 6.87 - 6.86 (1H, m), 5.75 (2H, s), 3.69 (2H, s), 1.92 (3H, s); Anal.

Calcd for Cl6HisN~OS ~ 0.2 H20: C, 53.83; H, 4.35, N, 27.46. Found: C, 53.74;

H, 4.29; N, 27.13.

mp 231.6 - 231.7 C; IR v~X (DR)/cni l 3642, 3320, 3198, 1727, 1533, 1437, 1223, 1029, 842 and 639; NMR SH (400 MHz, DMSO) 8.18 (1H, d, J 7.5 Hz), 8.13 (1H, s), 8.00 - 7.93 (2H, m), 7.91 (1H, d, J 3.5 Hz), 7.89 - 7.82 (1H, m), 7.34 (2H, br s), 6.87 (1H, dd, J 3.5, 1.5 Hz) and 6.01 (2H, s).

NMR SH (400 MHz, DMSO) 2.19 (3H, s), 3.50 (3H, s), 5.58 (2H, s), 6.84 - 6.97 236 AX 32 (3H, m), 7.08 (1H, d, J 8.0 Hz), 7.20 (1H, t, J
7.5 Hz), 7.35 (2H, s), 7.58 (1H, s), 7.91 (1H, d, J 3.0 Hz), 8.13 (1H, s) and 10.14 (1H, s); retention time 0.97 min.

mp 259.3 - 259.4 C; IR v~X (DR)/cni 13323, 3202, 1607, 1511; NMR 8H (400 MHz, DMSO) 8.12 - 8.11 (2H, m), 7.91 (2H, dd, J
1.0, 3.5 Hz), 7.70 - 7.66 (2H, m), 7.30 (4H, br s), 7.10 (4H, d, J 8.0 Hz), 6.85 (2H, dd, J 1.5, 3.5 Hz), 5.73 (4H, s), 4.23 (4H, s), 2.78 (3H, s).

mp 238.2 -238.6 C; IR v~X (DR)/cni 13189, 2908, 1653, 1592, 1470; NMR SH

(400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.91 (1H, d, J 3.0 Hz), 7.85 (1H, t, J 7.5 Hz), 7.43 (1H, d, J 7.5 Hz), 7.30 (2H, br s), 7.23 (1H, d, J7.5 Hz), 6.87 - 6.85 (1H, rn), 5.81 (2H, s), 4.56 (2H, s), 2.87 (3H, s).

mp 205.8 - 206.0 C; IR v~X (Nujol)/cmyl 3502, 3304, 3185, 2923, 1628, 1510;

NMR 8H (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.92 (1H, d, J 3.0 Hz), 7.83 (1H, t, J 8.0 Hz), 7.33 (1H, d, J 8.0 Hz), 7.30 (2H, br s), 7.17 (1H, d, J 8.0 Hz), 6.87 - 6.86 (1H, m), 5.79 (2H, s), 4.31 (2H, s), 2.84 (3H, s), 2.67 (3H, s); Anal.

Calcd for C17H18N803S: C, 49.27; H, 4.38, N, 27.02.
Found: C, 49.14; H, 4.49;

N, 26.74.

mp 254.3 - 254.5.C;1R v,i,aX (DR)/crti 13443, 3342, 3187, 1647, 1593, 1513, 1414, 1300, 1268 and 1225; NMR 8H (400 MHz, DMSO) 7.37 (2H, s), 6.96 (1H, t, J 7.8 Hz), 6.46 (1H, dd, J 1.0, J 8.0 Hz), 6.40 (2H, d, J 7.5 Hz), 6.33 (1H, s), 5.56 (2H, s), 5.2 (2H, s), 2.5 (3H,s) and 2.44 (3H, s).

NMR 8H (400 MHz, DMSO) 8.11 - 8.09 (1H, m), 7.89 - 7.86 (1H, dd, J 1.0, 3.5 Hz), 7.32 - 7.27 (2H, s), 7.22 - 6.95 (1H, t, J
9.0 Hz), 6.85 - 6.83 (1H, dd, J 2.0, 3.5 Hz), 6.35 - 6.29 (2H, m), 5.48 - 5.46 (2H, s) and 5.46 - 5.44 (2H, s);

Retention time 1.18 min.

IR v~X (DR)/cm~' 3850, 3667, 2923, 1730, 1601, 1464, 1023, 751 and 593; NMR

8H (400 MHz, DMSO) 3.68 (1H, dd, J 16.0, 5.5 Hz), 3.88 (1H, dd, J 16.0, .9.0 Hz), 6.05 (1H, dd, J 8.5, 5.5 Hz), 6.84 - 6.89 (1H, m), 7.29 (2H, s), 7.57 (1H, t, J

7.0 Hz), 7.72 (1H, d, J 7.5 Hz), 7.78 - 7.87 (2H, m), 7.91 (1H, d, J 3.5 Hz), 8.13 (1H, s). Anal. Calcd for C1~H12N60a ~ 0.2 HzO: C, 60.87; H, 3.72; N, 25.02.

Found: C, 60.89; H, 3.68; N, 24.85.

mp > 300 C dec; IR v~x (DR)/cni 1 3212, 2923, 1642, 1605, 1510, 1461, 1377, 1023 and 757; NMR ~H (400 MHz, DMSO) 11.16 (1H, br s), 8.12 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.44 - 7.36 (3H, m), 7.29 (1H, s), 6.86 (1H, dd, J 3.5, 1.5 Hz), 6.58 (1H, s), 6.42 - 6.38 (1H, m), 5'.87 (2H, s) and 2.27 (3H, s).

IR v",aX (Nujol)/crri 13319, 2924, 1646, 1606, 1462;
NMR 8H (400 MHz, DMSO) 244 BB 7 9.54 (1H, s), 8.27 - 8.26 (1H, m), 8.12 - 8.11 (1H, m), 7.90 (1H, d, J 3.5 Hz), 7.71 (1H, d, J 8.0 Hz), 7.32 (2H, br s), 7.17 -7.15 (1H, m), 7.11- 7.09 (1H, m), 6.86 - 6.85 (1H, m), 5.59 (2H, s), 2.18 (3H, s).

IR ymax (Nujol)/crri 13849 3500 3298 3174 2924 1698 1379. 1226, 1027, 953 and 753 NMR 8~ (400 MHz DMSO) 191 (3H d J 7 0 ~) 663 (1H, q, J 7.0 Hz) 6.84 - 6.87 (1H m) 7.32 (2H s~ 7 54 (2H t J 8 0 Hz), 7.66 (1H, tt, J 7.5, 2.0 Hz) 7.88 (1H d J 3 5 Hz) 7 98 - 8 03 (2H, m) 8 11 - 8.12 (lH,.m). Anal. Calcd for CI~HIdIV60~: C, 61.07; H. 4.22: N~25.12. Found:

C. 60.72; H, 4.27; N. 24.75.

IR v",aX (Nujol;)lcrri 1 3313, 3189, 2924, 1605, 1461, 1377, 1236, 1026 and 762;

NMR 8H (400 MHz, DMSO) 11.62 (1H, br s), 8.11 (1H, dd, J 2.0, 1.0 Hz), 7.90 (lH,d,J3.5Hz),7.41(lH,t,J2.5Hz),7.37-7.29(3H,m),6.94(lH,d,J11.0 Hz), 6.85 (1H, dd, J 3.5, 2.0 Hz) 6.52 - 6.47 (1H, m) and 5.71 (2H, s).

mp 134.5 - 134.6 C; IR v~X (Nujol)/crri 13306, 3189, 2924, 1635, 1610, 1580;

NMR ~H (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.92 - 7.91 (1H, m), 7.79 - 7.75 (1H, m), 7.35 (1H, d, J 8.0 Hz), 7.31 (2H, br s), 7.03 (1H, d, J 7.5 Hz), 6.86 (1H, 247 B 2g dd, J 3.5, 1.5 Hz), 5.74 (2H, s), 4.46 (2H, s), 3.65 (1H, sept, J 6.0 Hz), 1.12 (6H, d, J 6.0 Hz); Anal. Calcd for Cl$H19N~02 ~ 1.2 H20:
C, 55.86; H, 5.57, N, 25.33.

Found: C, 55.80; H, 5.41; N, 25.05.

mp 158.9. - 161.3 C; IR v~X (Nujol)/cmi 13301, 3185, 2923, 1636, 1611, 1570, 1536,1501, 1324 and 1210; NMR bH (400 MHz, DMSO) 7.88 (1H, d, J 3.0 Hz), 248 B 11 7.66(lH,t,J7.5Hz),7.27(2H,brs)7.18(lH, d,J7.5Hz),6.89(lH,d,J7.5 Hz), 6.51 (1H, dd, J 1.0, J 3.5 Hz), 5.71 (2H, s), 2.69 (2H, q, J7.5 Hz ), 2.46 (3H, s) and 1.15 (3H, J 7.5 Hz).

IR v,~x (DR;)/cmi' 3319, 2928, 1605, 1334, 1226, 1027, 737 arid 528; NMR 8H

(400 MHz, DMSO) 11.47 (1H, s), 8.14 - 8.09 (1H, m) 7.89 (1H, d, J 3.5 Hz), 7.48 (1H, d, J 3.0 Hz), 7.38 - 7.27 (3H, m), 6.94 (1H, d, J 13.0 Hz), 6.85 (1H, dd, J 3.5, 2.0 Hz), 6.52 - 6.47 ( 1H, m) and 5.81 (2H, s).

IR v",aX (DR)/crri 13318, 2923, 1640, 1579, 1455, 1377, 1079, 1022, 750 and 588;

~ SH (400 MHz, DMSO) 11.13 (1H, br s), 8.23 (1H, s), 8.05 - 8.04 (1H, m), 250 BE 6g 7.43 (lH,d, J 3.5 Hz), 7.30 (2H, s), 7.00 (1H, t, J 7.0 Hz), 6.90 (2H, s), 6.80 -6.77 (1H, m), 6.73 (1H, d, J 6.5 Hz), 6.51 (1H, sand 5.63 (2H, s).

mp 294.0 - 294.2 C; IR v~x (DR)/crri 13498, 3414, 1612, 1318, 1235, 102, 765 251 BE 42 and 589; NMR 8H (400 MHz, DMSO) 11.24 (1H, br s), 8.12 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.53 (1H, s), 7.39 (1H, t, J 2.5 Hz) 7.36 - 7.26 (3H, m), 6.88 - 6.82 (1H, m), 6.43 - 6.38 (1H, m) and 5.76 (2H, s) mp 200.2. - 201.2 C IR v",aX (DR)/cxri 1 3390, 3205, 2924, 1725, 1648, 1603, 1508, 1423, 1332, 1277 and 1158; NMR 8H (400 MHz, DMSO) 8.12 (1H, s), 252 BF 44 7.90 (1H, d, J 3.5 Hz), 7.35 - 7.25 (4H, m), 7.07 - 6.97 (3H, m), 6.86 (1H, dd, J

1.5, J 3.5 Hz), 6.45 (2H, t, J 7.5 Hz), 6.37 (1H, s), 6.32 (1H, t, J 6.0 Hz), 5.49(2H,. s) and 4.16 (2H, s; J 6.0 Hz).

mp 181.8 -182.1 C; IR v~X (DR)/crri 13362, 3208, 2988, 1654, 1601, 1513;

NMR SH (400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.91 (1H, d, J 3.5 Hz), 7.68 (1H, m), 7.29 (2H, br s), 6.87 - 6.85 (1H, m), 6.74 (1H, d, J 7.5 Hz), 6.68 (1H, d, J 8.0 Hz), 5.69 (2H, s), 4.07 (2H, q, J 7.0 Hz), 1.12 (3H, t, J 7.0 Hz).

mp 190.8 - 190.9 C; IR vI"aX (DR)/cni l 3514, 3292, 3158, 2984, 1615, 1500;

NMR 8H (400 MHz, DMSO) 7.88 (1H, d, J 3.5 Hz), 7.65 (1H, dd, J 7.0, 8.0 Hz), 7.25 (2H, br s), 6.72 (1H, d, J 7.0 Hz), 6.68 (1H, d, J 8.0 Hz), 6.52 - 6.50 (1H, m), 5.67 (2H, s), 4.08 (2H, q, J 7.0 Hz), 2.46 (3H, s), 1.12 (3H, t, J 7.0 Hz).

mp 184.5 -184.6 C; IR v~X (DR)/crri 13202, 1649, 1601, 1509, 1436, 1331, 1277 and 1221; NMR SH (400 MHz, DMSO) 8.43 (lH,d, J 4.89 Hz), 8.12 (1H, dd, J 0.8, 3.5 Hz) , 7.91( 1H, dd, J 0.9, 3.5 Hz), 7.65 (1H, td, J 1.7, 7.7 Hz), 7.30 255 BF 20 (2H, br s), 7.25 (1H, d, J7.9 Hz), 7.15 (1H, dd, J4.9, 7.5 Hz), 7.0 (1H, t, J7.8 Hz), 6.86 (1H, dd, J 1.7, 3.5 Hz), 6.48 - 6.36 (4H, m), 5.49 (2H, s), 4.27 (2H, s);

Anal. Calcd for CZ1H18N8O ~ 0.3 HBO : C, 62.46;
H, 4.64, N, 27.75. Found: C, 62.66; H, 4.57; N, 27.36.

Mp 167.6 -168.1 C. IR v~X (DR)/crri 13509, 3304, 3178, 1609, 1494, 1421, 1325, 1127, 839 and 752. NMR SH (400 MHz, DMSO) 2.05 (3H, d, J 7.0 Hz), 6.14 (1H, q, J 7.0 Hz), 6.84 - 6.88 (1H, m), 7.30 256 B 6 (2H, s), 7.52 (2H, d, J 8.5 Hz), 7.73 (2H, d, J 8.0 Hz), 7.91 (1H, dd, J 3.5, 1.0 Hz), 8.11- 8.13 (1H, m). Anal.

Calcd for C1~H13N6F30: C, 54.55; H, 3.50; N, 22.44.
Found: C, 54.52; H, 3.65;

N, 22.06.

IR v~X (DR)/crri 13459, 3348, 3187, 2960, 1648, 1513, 1351, 1244, 1011, 837 and 759; NMR 8H (400 MHz, DMSO) 11.18 (1H, br s), 257 BE 75 8.11 (1H, s), 7.89 (1H, d, J 3.0 Hz), 7.42 (1H, d, J 7.5 Hz), 7.37 - 7.26 (3H, m), 7.21 (1H, d, J 11.0 Hz), 6.89 - 6.81 (1H, m), 6.43 - 6.37 (1H, s) and 5.72 (2H, s).

mp > 300 C dec; IR v",aX (DR)/crri 13441, 3318, 2990, 1612, 1285, 1083, 839 and 593; NMR 8H (400 MHz, DMSO) 11.29 (1H, br s), 8.12 (1H, s), 7.91 (1H, d, J 3.5 Hz), 7.41 - 7.29 (3H, m), 7.22 (1H, dd, J 10.0, 2.5 Hz), 6.90 (1H, dd, J 9.5, 2.5 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz), 6.30 (1H, s) and 5.79 (2H, s).

mp 228.4 - 228.5 C; NMR 8H (400 MHz, DMSO) 8.13 -8.12 (1H, m), 7.91 259 B 50 (1H, d, J 3.5 Hz), 7.34 (2H, br s), 7.18 (2H, s), 6.87 - 6.85 (1H, m), 5.67 (2H, s), 2.22 (6H, s).

mp 150.3 =151.0 C. IR vm-XX (DR)/cW 13510, 3306, 3183, 1633, 1495, 1423, 1240, 1029 and 753; NMR 8H (400 MHz, DMSO) 2.02 (3H, d. J 7.0 Hz), 6.05 L1H 9~ J 7.0 Hz), 6.83 - 6.88 ( 1H, m), 7.10 - 7.22 (3H, m), 7.30 (2H, s), 7.40 (1H, dt, J 8.0, 6.5 Hz). 7.91 (1H, dd. J 3.5, 1.0 Hz), 8.10 - 8.13 (1H, m). Anal.

Calcd for C16H,3N6OF ~ 0.25 H20: C, 58.44; H, 4.14;
N, 25.56. Found: C, 58.48;

H, 3.98; N, 25.40.

IR v~X (DR)/cni 1 3472, 3318, 3184, 2922, 1651, 1595, 1478, 1417, 1329, 1218, 1097, 1015, 870, 767and 545; NMR 8H (400 MHz, DMSO) 11.50 (1H, s), 8.11 (1H, s), 7.90 (1H, d, J 3.5 Hz), 7.47 (1H, s), 7.42 (1H, t, J 3.0 Hz), 7.33 (2H, s), 7.19 (1H, s), 6.86 - 6.84 (1H, m), 6.53 - 6.51 (1H, m), 5.71 (2H, s).

mp 250.1- 261.3 C; IR v",aX (DR)/cW 13325, 3205, 2968, 1603, 1488; NMR 8H

262 C 34 (400 MHz, DMSO) 8.11 - 8.10 (1H, m), 7.89 - 7.87 (1H, m), 7.28 (2H, br s), 6.85 - 6.83 (1H, m), 6.81 (2H, s), 5.40 (2H, s), 4.56 (2H, br s), 2.03 (6H, s).

IR Vmax (DR)/crri 12825, 2021, 1645, 1453 1394, 1286 1171. 1030 779 and 619;NMR 8H (400 MHz, DMSO) 2.02 (3H, d, J 7.0 Hzl, 6.07 (1H q J 7.0 Hz) 6.85 - 6.88 (1H, m), 7.13 - 7.18 (1H, m), 7.25 (1H, d, J 8.5 Hz), 7.36 (1H d, J

8.0 Hz), 7.47 (1H, t, J 7.5 Hz), 7.92 (1H, d, J 3.5 Hz), 8.12 - 8.14 (1H m). Anal.

Calcd for C~H~N~O ~ 2HC1 ~ 0.8 HBO: C. 47.02; H, 4.59; N, 23.99. Found: C, 46.87; H, 4.43; N, 23.71.

mp 162.0 -162.6 C; IR v",aX (DR)/crri 13319, 3206, 2932, 1644, 1505; NMR BH

(400 MHz, DMSO) 8.13 - 8.12 (1H, m), 7.92 - 7.91 (1H, m), 7.68 - 7.64 (1H, m), 264 B 26 7.31 (2H, br s), 7.21 (1H, d, J 7.5 Hz), 6.92 (1H, d, J 8.0 Hz), 6.86 (1H, dd, J 3.5, 1.5 Hz), 5.74 (2H, s), 3.58 (2H, t, J 6.5 Hz), 3.16 (3H, s), 2.84 (2H, t, J 6.5 Hz);

M/Z 352 (M+H)+.

NMR 8H (400 MHz, DMSO) 8.12 - 8.11 (1H, m), 7.92 - 7.90 (1H, m), 7.47 (1H, d, J 8.0 Hz), 7.28 (2H, br s), 6.91 (1H, d, J 8.0 Hz), 6.86 (1H, dd, J 2.0, 3.5 Hz), 5.73 - 5.69 (1H, m), 2.60 - 2.46 (2H, m), 2.39 (3H, s), 2.20 (3H, s), 0.87 (3H, t, J

7.0 Hz); M/Z 350 (M+H)+.

NMR Sn (400 MHz, DMSO) 8.22 - 8.17 (2H, m), 7.94 ( 1H, d, J 2.01 Hz), 7.73 -266 AK 99 7.63 (2H, m), 7.37 (1H, d, J 2.5 Hz) and 5.86 (2H, s); M/Z 338 (M+H)+;

Retention time 1.74 min.

mp 255.6 - 255.7 C; IR v,I,aX (DR)/ciri' 3512, 3294, 3179, 2960, 2692, 1745, 1638, 1432 and 1371; NMR SH (400 MHz, DMSO) 7.88 (1H, d, J 3.51 Hz), 7.81 ( 1H, dd, J 1.0, J 8.0 Hz), 7.46 - 7.29 (2H, br s), 7.40 ( 1H, t, J 7.8 Hz) , 7.23 ( 1H, d, J 8.0 Hz), 6.51 (1H, dd, J 1.0, 3.5 Hz), 5.78 (2H, s) and 2.46 (6H, s).

mp 248.1- 249.0 C IR v~X (DR)/crri' 3507, 3308, 3190, 2952, 1626,.1571, 1519, 1434, 1348 and 1291; NMR 8H (400 MHz, DMSO) 8.22 (2H, d, J 8.5 Hz), 7.89(1H, d, J 3.5 Hz), 7.49 (2H, d, J 9.0 Hz), 7.36 (2H, br s), 6.52 (1H, dd, J 1.0, 3.5 Hz), 5.83 (2H, s) and 2.46 (3H, s).

NMR SH (400 MHz, DMSO) 8.14 - 8.12 (1H, m), 7.92 - 7.90 (1H, dd, J 1.0, 3.5 269 B 18 Hz), 7.42 - 7.34 (2H, s), 7.26 - 7.25 (4H, s), 6.87 - 6.85 (1H, dd, J 1.5, 3.5 Hz), 5.66 - 5.64 (2H, s), 3.15 - 3.13 (3H, s) and 1.38 - 1.36 (9H, s).

NMR 8H (400 MHz, DMSO) 8.22 - 8.13 (2H, m), 7.75 - 7.65 (3H, m), 7.59 (1H, dd, J 1.5, J 3.0 Hz), 7.34 (2H, br s), 6.96 (1H, dd, J 1.5, J 3.5 Hz), 6.45 (1H, t, J

3.2 Hz), 5.85 (2H,s) and 1.22 (9H, s); M/Z 437 (M+H)+;
Retention time 4.36 min.

NMR 8H (400 MHz, DMSO) 8.21- 8.17(2H, m), 7.71-7.63 (2H, m), 7.48 (2H, 271 Q 40 br s), 5.87 (2H, s), 2.50 (3H, s) and 2.44 (3H, s); M/Z 383 (M+H)~; Retention time 3.69 min..

' NMR 8H (400 MHz, DMSO) 8.18 (1H, dd, J 9.6, 2.0 Hz), 8.13 (1H, d, J 1.6 Hz), 272 B 8.05 (1H, dd, J 8.4, 2.4 Hz), 7.90 (1H, d, J 3.2 Hz), 7.45 (1H, t, J 8.0 Hz), 7.38 (2H, br s), 6.86 (1H, dd, J 3.6, 2.0 Hz) and 5.84 (2H, s).

NMR 8H (400 MHz, DMSO) 8.13 - 8.09 (1H, m), 7.89 (1H, d, J 3.5 Hz), 7.66 273 B (1H, d, J 3.5 Hz), 7.39 (1H, s), 7.29 (2H, br s), 6.85 (1H, dd, J 3.5, 2.0 Hz), 6.68 (1H, d, J 3.5 Hz), 6.65 (1H, s), 2.27 (3H, s) and 1.52 (9H, s).

IR v~X (Nujol)/cni 1 3313, 2923, 1693, 1603; NMR
8H (400 MHz, DMSO) 8.78 (1H, br s), 8.12 - 8.11 (1H, m), 7.90 (1H, d, J
3.5 Hz), 7.34 - 7.31 (3H, m), 7.13 -7.12 (1H, m), 7.08 - 7.05 (1H, m), 6.86 - 6.85 (1H, m), 5.58 (2H, s), 4.08 (2H, q, J 7.0 Hz), 2.16 (3H, s), 1.21 (3H, t, J 7.0 Hz).

Adenosine Receutor Binding Binding Affinities at liA2A Receptors The compounds were examined in an assay measuring ire vitro binding to human adenosine AaA receptors by determining the displacement of the adenosine AaA receptor selective radioligand [3H]-CGS 21680 using standard techniques. The results are summarised in Table 3.
Table 3 Example K; (nM) Example 3 3 Example 4 4 Example 5 3 Example 8 3 Example 11 2 Example 12 7 Example 13 2 Example 15 4 Example 41 2 Example 57 2 Example 78 3 Example 92 2 Example 107 2 Example 120 1 Example 149 1 Example 156 2 Example 169 2 Example 188 1 Example 202 1 Example 209 1 Example 221 2 Example 233 4 Example 255 4 Evaluation of uotential anti-Parkinsonian activity in vivo Haloperidol-induced hypolocomotion model It has previously been demonstrated that adenosine antagonists, such as theophylline, can reverse the behavioural depressant effects of dopamine antagonists, such as haloperidol, in rodents (Mandhane S.N. et al., Adenosine A2 receptors modulate haloperidol-induced catalepsy in rats. Eur. J. Pharniacol. 1997, 328, 135 - 141). This approach is also considered a valid method for screening drugs with potential antiparkinsonian effects.
Thus, the ability of novel adenosine antagonists to block haloperidol-induced deficits in locomotor activity in mice can be used to assess both in vivo and potential antiparkinsonian efficacy.
Method Female TO mice (25-30g) obtained from TUCK, UK, are used for all experiments.
Animals are housed in groups of 8 [cage size - 40 (width) x 40 (length) x 20 ( height)cm]
under l2hr lightldark cycle (lights on 08:OOhr), in a temperature (20 ~
2°C) and humidity (55 ~ 15%) controlled environment. Animals have free access to food and water, and are allowed at least 7 days to acclimatize after delivery before experimental use.
Drugs Liquid injectable haloperidol (1 ml Serenance ampoules from Baker Norton, Harlow, Essex, each containing haloperidol BP 5 mg, batch # P424) are diluted to a final concentration of 0.02 mglml using saline. Test compounds are typically prepared as aqueous suspensions in 8% Tween. All compounds are administered intraperitoneally in a volume of 10 ml/kg.

Procedure 1.5 hours before testing, mice are administered 0.2 mglkg haloperidol, a dose that reduces baseline locomotor activity by at least 50%. Test substances are typically administered 5-60 minutes prior to testing. The animals are then placed individually into clean, clear polycarbonate cages [20 (width) x 40 (length) x 20 (height) cm , with a flat perforated, Perspex lid]. Horizontal locomotor activity is determined by placing the cages within a frame containing a 3 x 6 array of photocells linked to a computer, which tabulates beam breaks. Mice are left undisturbed to explore for 1 hour, and the number of beams breaks made during this period serves as a record of locomotor activity which is compared with data for control animals for statistically significant differences.
6-OHDA Model Parkinson's disease is a progressive neurodegenerative disorder characterised by symptoms of muscle rigidity, tremor, paucity of movement (hypokinesia), and postural instability. It has been established for some time that the primary deficit in PD is a loss of dopaminergic neurones in the substantia nigra which project to the striatum, and indeed a substantial proportion of striatal dopamine is lost (ca 80-85%) before symptoms are observed. The loss of striatal dopamine results in abnormal activity of the basal ganglia, a series of nuclei which regulate smooth and well co-ordinated movement (Blandini F. et al., Glutamate and Parkinson's Disease. Mol. Neurobiol. 1996, 12, 73 - 94). The neurochemical deficits seen in Parkinson's disease can be reproduced by local injection of the dopaminergic neurotoxin 6-hydroxydopamine into brain regions containing either the cell bodies or axonal fibres of the nigrostriatal neurones.
By unilaterally lesioning the nigrostriatal pathway on only one-side of the brain, a behavioural asymmetry in movement inhibition is observed. Although unilaterally-lesioned animals are still mobile and capable of self maintenance, the remaining dopamine-sensitive neurones on the lesioned side become supersenstive to stimulation. This is demonstrated by the observation that following systemic administration of dopamine agonists, such as apomorphine, animals show a pronounced rotation in a direction contralateral to the side of lesioning. The ability of compounds to induce contralateral rotations in 6-OHDA lesioned rats has proven to be a sensitive model to predict drug efficacy in the treatment of Parkinson's Disease.

Animals Male Sprague-Dawley rats, obtained from Charles River, are used for all experiments.
Animals are housed in groups of 5 under l2hr light/dark cycle (lights on 08:OOhr), in a temperature (20 ~ 2°C) and humidity (55 ~ 15%) controlled environment.
Animals have free access to food and water, and are allowed at least 7 days to acclimatize after delivery before experimental use.
D
Ascorbic acid, desipramine, 6-OHDA and apomorphine (Sigma-Aldrich, Poole, UK).

OHDA is freshly prepared as a solution in 0.2% ascorbate at a concentration of 4 mglmL
prior to surgery. Desiprarnine is dissolved in warm saline, and administered in a volume of 1 mllkg. Apomorphine is dissolved in 0.02% ascorbate and administered in a volume of 2 mL/kg. Test compounds are suspended in 8%Tween and injected in a volume of 2 mL/kg.
S_ urgerY
15 minutes prior to surgery, animals are given an intraperitoneal injection of the noradrenergic uptake inhibitor desipramine (25 mglkg) to prevent damage to non-dopamine neurones. Animals are then placed in an anaesthetic chamber. and anaesthetised using a mixture of oxygen and isoflurane. Once unconscious, the animals are transferred to a stereotaxic frame, where anaesthesia is maintained through a mask. The top of the animal's head is shaved and sterilised using an iodine solution. Once dry, a 2 cm long incision is made along the midline of the scalp and the skin retracted and clipped back to expose the skull. A small hole is then drilled through the skill above the injection site. In order to lesion the nigrostriatal pathway, the injection cannula is slowly lowered to position above the right medial forebrain bundle at -3.2 mm anterior posterior, -1.5 mm medial lateral from bregma, and to a depth of 7.2 mm below the duramater. 2 minutes after lowing the cannula, 2 ~,L of 6-OHI~A is infused at a rate of 0.5 p.L,/min over 4 minutes, yeilding a final dose of 8 ~,g. The cannula is then left in place for a further 5 minutes to facilitate diffusion before being slowly withdrawn. The skin is then sutured shut using Ethicon W501 Mersilk, and the animal removed from the strereotaxic frame and returned to its homecage. The rats are allowed 2 weeks to recover from surgery before behavioural testing.

Apparatus Rotational behaviour is measured using an eight station rotameter system provided by Med Associates, San Diego, USA. Each station is comprised of a stainless steel bowl (45 cm diameter x 15 cm high) enclosed in a transparent Plexiglas cover running around the edge of the bowl, and extending to a height of 29 cm. To assess rotation, rats are placed in cloth jacket attached to a spring tether connected to optical rotameter positioned above the bowl, which assesses movement to the left or right either as partial (45°) or full (360°) rotations.
All eight stations are interfaced to a computer that tabulated data.
Procedure ~ ' To reduce stress during drug testing, rats are initially habituated to the apparatus for 15 minutes on four consecutive days. On the test day, rats are given an intraperitoneal injection of test compound 30 minutes prior to testing. Immediately prior to testing, animals are given a subcutaneous injection of a subthreshold dose of apomorphine, then placed in the harness and the number of rotations recorded for one hour. The total number of full contralatral rotations during the hour test period serves as an index of antiparkinsonian drug efficacy.

Claims (64)

1. The use of a compound of formula (I):

wherein R1 is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR5R6, NR4COR5, NR4CONR5R6, NR4CO2R7 and NR4SO2R7;
R2 is selected from aryl attached via an unsaturated carbon;
R3 is selected from H, alkyl, COR5, CO2R7, CONR5R6, CONR4NR5R6 and SO2R7;
R4, R5 and R6 are independently selected from H, alkyl and aryl or where R5 and R6 are in an NR5R6 group, R5 and R6 may be linked to form a heterocyclic group, or where R4, R5 and R6 are in a (CONR4NR5R6) group, R4 and R5 may be linked to form a heterocyclic group; and R7 is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, in the manufacture of a medicament for the treatment or prevention of a disorder in which the blocking of purine receptors may be beneficial.

2. Use according to claim 1 wherein R1 is selected from alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR5R6, NR4COR5, NR4CONR5R6, NR4CO2R7 and NR4SO2R7.

3. Use according to claim 1 wherein R1 is selected from alkyl, alkoxy, alkylthio, NR5R6, NR4COR5, NR4CONR5R6, NR4CO2R7 and NR4SO2R7.

4. Use according to claim 1 wherein R1 is selected from NR5R6, NR4COR5, NR4CONR5R6, NR4CO2R7 and NR4SO2R7.

5. Use according to claim 1 wherein R1 is selected from NR5R6.

6. Use according to claim 1 wherein R1 is NH2.

7. Use according to claim 1 wherein R1 is selected from haloalkyl and arylalkyl.

8. Use according to any preceding claim wherein R2 is not ortho,ortho-disubstituted.

9. Use according to any preceding claim wherein R2 is not substituted at either ortho position.

10. Use according to any preceding claim wherein R2 is a heteroaryl group.

11. Use according to claim 10 wherein R2 is a heteroaryl group which is attached to the pyrimidine ring of formula (I) such that a heteroatom is adjacent to the unsaturated carbon atom attached to said pyrimidine ring.

12. Use according to claim 10 or 11 wherein R2 is an N, O or S-containing heteroaryl group.

13. Use according to any of claims 10 to 12 wherein R2 is selected from furyl, thienyl, pyridyl, thiazolyl, pyrazolyl, triazolyl, pyrrolyl and oxazolyl.

14. Use according to any of claims 10 to 12 wherein R2 is selected from 2-furyl, 2-thienyl, 2-thiazolyl, 2-pyridyl, 3-pyrazolyl, 2-pyrrolyl, 4-triazolyl and 5-oxazolyl.

15. Use according to any of claims 10 to 12 wherein R2 is selected from furyl, thienyl, pyridyl, thiazolyl and pyrazolyl.

16. Use according to any of claims 10 to 12 wherein R2 is selected from 2-furyl, 2-thienyl, 2-thiazolyl, 2-pyridyl and 3-pyrazolyl.

17. Use according to any of claims 10 to 12 wherein R2 is 2-furyl.

18. Use according to any of claims 1 to 9 wherein R2 is phenyl.

19. Use according to any preceding claim wherein R3 is selected from H and substituted alkyl.

20. Use according to claim 19 wherein R3 is selected from alkyl substituted by aryl, cycloalkyl, non-aromatic heterocyclyl, CN, CO2R5, CONR5R6, CONR4NR5R6 or C(=NR4)NR5R6.

21. Use according to claim 19 wherein R3 is selected from alkyl substituted by aryl.

22. Use according to claim 21 wherein R3 is selected from (CR9R10)n R11 wherein n is 1 to 6, R9 and R10 are independently selected from H, alkyl and aryl, and R11 is selected from the group consisting of substituted aryl (including heteroaryl) groups.

23. Use according to claim 22 wherein R11 is selected from mono-, di- or tri-substituted aryl groups represented by the formula Ar(R12)a(R13)b(R14)c wherein Ar is an aryl group;
wherein R12, R13 and R14 are substituent group(s), the same or different; and wherein a, b and c are 0 or 1 such that a+b+c >=1.

24. A use according to claim 22 or 23 wherein n is 1 to 3.

25. A use according to claim 22 or 23 wherein n is 1.

26. A use according to any of claims 22 to 25 wherein the or each R9 and R10 are selected from H and alkyl.

27. A use according to any of claims 22 to 25 wherein at least one of the or each R9 and R10 is H.

28. A use according to any of claims 22 to 25 wherein both the or each R9 and R10 are H.

29. Use according to any of claims 23 to 28 wherein R12, R13 and R14 are independently selected from NR5R6, alkyl, alkoxy, halogen, NO2, CN, hydroxy, NHOH, CHO, CONR5R6, CO2R5, NR4COR5, NR4CO2R7, NR4SO2R7, OCO2R7 and aryl.

30. Use according to any of claims 23 to 28 wherein R12, R13 and R14 are independently selected from NR5R6, alkyl and halogen.

31. Use according to claim 29 or 30 wherein R12, R13 and R14 are independently selected from alkyl, and said alkyl is substituted alkyl and is selected from alkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl.

32. Use according to claim 29 or 30 wherein R12, R13 and R14 are independently selected from unsubstituted alkyl, NH2 and fluoro.

33. A use according to any of claims 22 to 32 wherein said substituted aryl group R11 or Ar is selected from phenyl, pyridyl, indolyl, furyl, thienyl, isoindolyl, indolinyl, isoxazolyl, oxazolyl, thiazolyl, pyrazinyl, pyrimidinyl, quinolinyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl, indazolyl, benzodioxolyl and dihydrobenzofuranyl.

34. Use according to any of claims 22 to 32 wherein said substituted aryl group R11 or Ar is selected from phenyl, pyridyl, indolyl, furyl and thienyl.

35. Use according to claim 34 wherein said substituted aryl group R11 or Ar is selected from phenyl, thienyl, furyl and pyridyl.

36. Use according to claim 34 wherein said substituted aryl group R11 or Ar is selected from phenyl, 2-thienyl, 2-furyl and 2-pyridyl.

37. Use according to any of claims 1 to 18 wherein R3 is selected from (CR9R10)n R8 wherein n is 1 to 6, R9 and R10 are independently selected from H, alkyl and aryl, and R8 is selected from cycloalkyl, non-aromatic heterocyclic, CN, CO2R5, CONR5R6, and C(=NR4)NR5R6.

38. Use according to claim 37 wherein n, R9 and R10 are as set out in any claims 24 to 28

39. Use according to claim 37 wherein R8 is selected from CONR5R6, R5 is hydrogen and R6 is selected from unsubstituted alkyl and arylalkyl.

40. Use according to any of claims 1 to 18 wherein R3 is selected from CONR5R6, R5 is H
and R6 is selected from arylalkyl, preferably arylmethyl.

41. Use according to claim 1 wherein the compound is selected from:
7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine methyl 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methylbenzoate 3-(3,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-chloro-2-thienyl)methyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)phenyl-(1-methyl-1H-imidazol-4-yl)sulphonamide 5-amino-N-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylcarboxamide 7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine ethyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate 3-(3-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-(3-pyridyl)propyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-trifluoromethylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-hydroxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(5-methyl-2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(1H pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid 3-(3-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-methyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetamide (5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(3-chlorophenyl)acetamide 7-(2-furyl)-3-(6-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrirnidine-5-amine 3-(2-fluorobenzyl)-7-(5-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate 3-(2,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2,6-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(4-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-thienyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 6-chloro-N-(7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)pyridine-3-carboxamide 3-(3-nitrobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N,N-dimethylbenzamide 3-(3-aminobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-methylbenzamide 3-(3-aminobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluoro-5-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(2-pyridyl)acetamide (5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(2-pyridylmethyl)acetamide (5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-phenylacetamide 3-(3,5-dinitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(5-methyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2,3-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2,4-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(5-methyl-2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2,6-difluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(5-methyl-2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-chlorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(4-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2,5-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-methoxy-5-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-methylbenzamide N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide 3-(2-fluorobenzyl)-7-(5-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-chloro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-fluoro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-methoxybenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl N-(3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate 3-(2-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 3-(3,5-diaminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminomethylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 7-(2-furyl)-3-(2-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluoro-5-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluorobenzyl)-7-(1H-triazol-4-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-chloro-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(5-methyl-2-furyl)-3-(6-phenyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-amino-2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)-3-methylbutanamide 7-(5-methyl-2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-hydroxylamino-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-amino-2-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-amino-4-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3,5-dimethylisoxazol-4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-cyclohexylmethyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(5-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzoic acid 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzamide 7-(2-furyl)-3-(2-methylthiazol-4-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminomethylbenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-isopropyl-N-methylbenzamide 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-isopropylbenzamide 3-(2-amino-5-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-cyano-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(5-methyl-2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(8-quinolinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-phenylthiazol-4-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(4-methyl-2-thiazolyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-chloro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(1,2,5-benzoxadiazol-5-yl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-methoxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-amino-4-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(4-hydroxylamino-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-methyl-4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(4-hydroxylamino-6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-chloro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-amino-4-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3,4-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine trifluoroacetate salt 7-(5-methyl-2-furyl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-amino-3-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(5-methyl-3-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-methyl-4-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(1,2,5-benzothiadiazol-4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-fluoro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-nitrobenzyl)-7-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(4-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl N-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-4-pyridylmethyl)carbamate 7-(2-furyl)-3-(3-methoxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-ethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-ethyl-4-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate tert-butyl 4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate 7-(2-furyl)-3-(4-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate 3-(4-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl 5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate.
tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-2-fluorophenyl)carbamate 3-(4-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(5-ethyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl 6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate 3-(4-amino-3-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl (4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-3,5-difluorophenyl)carbonate 3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminobenzyl)-7-(5-ethyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminobenzyl)-7-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(5-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-fluoro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2,6-difluoro-4-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl N-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate 3-(1H-benzotriazol-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-methoxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)phenylacetamide 3-(2-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-(N,N-dimethylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-difluoromethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-phthalimidomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-amino-4-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2,3-dihydrobenzofuran-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-bromo-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2,3,5-trifluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluoro-5-iodobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-furylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-amino-5-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl (5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-2-nitrophenyl)carbonate 3-(4-amino-3-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3)triazolo[4,5-d]pyrimidine-5-amine 3-(4-amino-3-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-aminobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d)pyrimidine-5-amine 7-(2-furyl)-3-(3-hydroxy-4-nitrobenzyl)-3H-[1,2,3]triazolo(4,5-d]pyrimidine-5-amine N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)acetamide N-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide 7-(2-furyl)-3-(3-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-amino-2-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-methyl-2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-allyloxymethyl-2-pyridylmethyl)- N,N-diallyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-methoxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-allyloxymethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-allyloxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-(1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3-isopropyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(quinolin-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(4-(N-methylamino)benzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(6-methyl-2-pyridyl)propanone 3-(3-aminobenzyl)-7-(1H-pyrrol-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-nitrobenzyl)-7-(2-pyridyl)-3H-[1,2,3)triazolo[4,5-d]pyrimidine-5-amine N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)acetamide 7-(2-furyl)-3-(4-nitro-2-(2-trimethylsilylethoxy)methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-ethyl-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-(2-thienylethyl))-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-isopropyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(1-(2H-tetrahyropyran-2-yl)indazol-5-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4,6-diisopropyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(5-indazolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(2-hydroxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-vinyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-carboxylate tert-butyl 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate 6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)pyridine-carboxaldehyde tert-butyl 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate 3-(2-indolylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-ethyl-2-thienylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(3,4-methylenedioxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-amino-3-ethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylethanone N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)thiophene-2-carboxamide 7-(2-furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)-3,3-dimethylbutanamide N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)cyclopropanecarboxamide 7-(2-furyl)-3-(6-n-propyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-isobutyloxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo [4,5-d]pyrimidine-5-amine 3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-amino-3-isopropylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-cyanomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-nitrophenyl)ethanone 4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetyl)-benzonitrile N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)propanesulphonamide N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-5-chloro-2-thiophenesulphonamide 7-(2-furyl)-3-(6-(N-methylamino)methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-(N,N-diethylamino)phenyl)ethanone 7-(2-furyl)-3-(6-isopropyl-3-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d)pyrimidin-3-yl)-1-(4-methoxyphenyl)ethanone tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-chloroindole-1-carboxylate 3-(5-chloro-7-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-3,5-dimethylisoxazol-4-ylsulphonamide 3-(6-(N,N-dimethylamino)methyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-methylthiomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(2-nitrophenyl)ethanone N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-1,2-dimethyl-1H-imidazol-4-ylsulphonamide N,N-bis(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-pyridylmethyl) methanesulphonamide 7-(2-furyl)-3-(6-methylsulphonylmethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)-N-methyl methanesulphonamide 3-(3-aminobenzyl)-7-(4,5-dimethyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-indanone 7-(2-furyl)-3-(5-methyl-7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-methylphenyl)formamide 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylpropanone 3-(7-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-isopropoxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-ethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(7-bromo-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-(4-fluorobenzylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-ethoxy-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-ethoxy-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-(2-pyridylmethylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(1-(4-trifluoromethylphenyl)ethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(6-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(5-fluoro-2-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3,5-dimethyl-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(1-(3-fluorophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(7-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(4-amino-3,5-dimethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(1-(3-aminophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(6-(2-methoxyethyl)-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(2-furyl)-3-(1-(5,6-dimethyl-2-pyridyl)propyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(3-nitrobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 7-(5-methyl-2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 7-(5-methyl-2-furyl)-3-(4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)phenyl)-N-methylcarbamate tert-butyl 2-(5-amino-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)pyrrole-1-carboxylate 7-(4,5-dimethylthiazol-2-yl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 3-(2-fluoro-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-methylindole-1-carboxylate, and ethyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)-2-methylphenyl)carbamate.

42. Use according to claim 1 wherein the compound is selected from: 3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;
7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;
3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;
3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;
7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;
7-(2-furyl)-3-(2-nitrobenzyl)-3H-[1,2,3 ]triazolo[4,5-d]pyrimidine-5-amine;
3-(2-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine; and 3-(3-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine.

43. A method of treating or preventing a disorder in which the blocking of purine receptors may be beneficial comprising administration to a subject in need of such treatment an effective dose of a compound as set out in any one of claims 1 to 42 or a pharmaceutically acceptable salt thereof.

44. A use or method according to any preceding claim wherein the disorder is caused by the hyperfunctioning of purine receptors.

45. A use or method according to any preceding claim wherein the purine receptors are adenosine receptors.

46. A use or method according to claim 45 wherein the adenosine receptors are receptors.

47. A use or method according to any preceding claim wherein the disorder is a movement disordert.

48. A use or method according to claim 47 wherein the movement disorder is Parkinson's disease.

49. A use or method according to claim 48 for treatment of drug-induced Parkinsonism, post-encephalitic Parkinsonism, Parkinsonism induced by poisoning or post-traumatic Parkinson's disease.

50. A use or method according to claim 47 wherein the movement disorder is progressive supernuclear palsy, Huntingtons disease, multiple system atrophy, corticobasal degeneration, Wilsons disease, Hallerrorden-Spatz disease, progressive pallidal atrophy, Dopa-responsive dystonia-Parkinsonism, spasticity or other disorders of the basal ganglia which result in dyskinesias.

51. A use or method according to any one of claims 47 to 50 wherein the compound of formula (I) is in combination with one or more additional drugs useful in the treatment of movement disorders, the components being in the same formulation or in separate formulations for administration simultaneously or sequentially.

52. A use or method according to claim 51 wherein said additional drug(s) useful in the treatment of movement disorders is/are a drug useful in the treatment of Parkinson's disease.

53. A use or method according to claim 51 or 52 wherein the or one of the additional drugs is L-DOPA or a dopamine agonist.

54. A use or method according to any one of claims 1 to 46 wherein said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy.

55. A use or method according to claim 54 wherein said cognitive or memory impairment disorder is Alzheimer's disease.

56. Use of a compound as set out in any one of claims 1 to 42 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for neuroprotection in a subject.

57. A method of neuroprotection comprising administration to a subject in need of such treatment an effective dose of a compound as set out in any one of claims 1 to 42 or a pharmaceutically acceptable salt thereof.

58. A use or method according to claim 56 or 57 wherein said medicament or said method is for neuroprotection in a subject suffering from or at risk from a neurodegenerative disorder.

59. A use or method according to claim 58 wherein said neurodegenerative disorder is a movement disorder.

60. A use or method according to claim 59 wherein said movement disorder is a disorder as set out in claim 48, 49 or 50.

61. A use or method according to any one of claims 1 to 60 wherein the subject is human.

62. A compound as set out in any one of claims 1 to 42, or a pharmaceutically acceptable salt or prodrug thereof, for use in therapy.

63. A compound as set out in any one of claims 1 to 42, per se, other than compounds wherein R1 is H and R3 is methyl.

64. A compound according to claim 63 other than compounds wherein R3 is methyl.