WO1987003807A1 - Oxazole derivatives and their use as anti-hyperglycaemic - Google Patents
Oxazole derivatives and their use as anti-hyperglycaemic Download PDFInfo
- Publication number
- WO1987003807A1 WO1987003807A1 PCT/GB1986/000789 GB8600789W WO8703807A1 WO 1987003807 A1 WO1987003807 A1 WO 1987003807A1 GB 8600789 W GB8600789 W GB 8600789W WO 8703807 A1 WO8703807 A1 WO 8703807A1
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- WIPO (PCT)
- Prior art keywords
- methyl
- compound
- formula
- oxazolyl
- chlorophenyl
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A method for the treatment and/or prophylaxis of hyperglycaemia in humans or non-human mammals, which method comprises the administration of an effective, non-toxic amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester or amide thereof, wherein R1 represents a C1-6 alkyl, C1-6 alkylaryl or aryl group; R2 represents a hydrogen atom or a C1-6 alkyl group; R3 represents a substituted or unsubstituted aryl group; and n represents an integer of from 1 to 6; and certain compounds and pharmaceutical compositions for use in such method.
Description
Oxazole derivatives and their use as anti-hyperglycaemic.
The invention relates to a method for the treatment and/or prophylaxis of hyperglycaemia and compounds for use in such method.
Japanese Published Application No. 0051111 discloses oxazoles of formula (A):
The oxazoles of formula (A) and salts thereof are disclosed as having good serum-cholesterol and serum-triglyceride level lowering activity and good platelet-agglutination inhibitory activity, being useful as anti-lipaemic agents.
It has now surprisingly been discovered that certain oxazoles, including the compounds of formula (A), have useful anti hyperglycaemic activity.
Accordingly, the present invention provides a method for the treatment and/or prophylaxis of hyperglycaemia
in humans or non-human mammals, which method comprises the administration of an effective, non-toxic amount of a compound of formula (I):
R1 represents a C1-6 alkyl, C1-6 arylalkyl or aryl group; R2 represents a hydrogen atom or a C1-6 alkyl group; R3 represents a substituted or unsubstituted aryl group, and n represents an integer of from 1 to 6.
When R1 represents an aryl group it is suitably a phenyl group.
When R3 represents an aryl group it is suitably a phenyl group, preferably substituted with up to two halogen atoms.
Favourably, n represents an integer of from 1 to 4, preferably 1, 2 or 3.
In a further aspect, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt, ester or amide thereof, for use in the manufacture of a medicament for the treatment and/or prophylaxis of hyperglycaemia in humans or non-human mammals.
The present invention also provides a pharmaceutical composition for use in the treatment and/or prophylaxis
of hyperglycaemia in humans or non-human mammals which comprises an effective, non-toxic amount of a compound of formula (I), or a pharmaceutically acceptable salt, ester or amide thereof, and a pharmaceutically acceptable carrier therefor.
Certain of the compounds of formula (I) are novel compounds, accordingly the present invention provides a compound of formula (II):
or a pharmaceutically acceptable salt, ester or amide thereof, wherein
R4 represents a C1-6 alkyl, C1 -6 arylalkyl or aryl group;
R5 represents a hydrogen atom or a C1-6 alkyl group;
R6 represents a substituted or unsubstituted aryl group; and m represents an integer of from 1 to 6; providing that when R4 represents lower alkyl, R5 represents a hydrogen atom or lower alkyl and m represents 1; then R6 does not represent a phenyl group or a phenyl group substituted with a halogen atom.
When R4 represents an aryl group it is suitably a phenyl group.
When R6 represents an aryl group it is suitably a phenyl group substituted with up to two halogen atoms. Preferably, R3 or R6 represent 4-chlorophenyl or 2,4-dichlorophenyl.
Preferably, R1 or R4 represents a group selected from the group consisting of: methyl, ethyl, n-propyl or phenyl. Preferably, R2 or R5 represent a methyl group.
Suitable aryl groups, or aryl moieties as for example in the C1-6 alkylaryl group, include substituted or unsubstituted phenyl or naphthyl groups.
Suitably, when substituted the aryl group may be substituted with up to five, favourably up to three, groups selected from halogen, C1-6 alkyl, phenyl, C1-6 alkoxy, halo C1-6 alkyl, hydroxy, amino, nitro, carboxy C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy or C1-6 alkylcarbonyl groups.
When used herein the term 'lower alkyl' relates to C1-6 alkyl groups.
When used herein the term 'C1-6 alkyl' or the term 'C1-6 alk' relate to the groups or moieties comprising straight and branched chain alkyl groups containing from 1 to 6 carbon atoms, such as methyl, ethyl, propyl and butyl.
When used herein the term 'halogen' refers to fluorine, chlorine, bromine and iodine, preferably chlorine.
Suitable pharmaceutically acceptable salts of carboxy groups include metal salts, such as for example aluminium, alkali metal salts such as sodium or potassium, alkaline earth metal salts such as calcium
or magnesium and ammonium or substituted ammonium salts, for example those with lower alkylamines such as triethylamine, hydroxy-lower alkylamines such as 2-hydroxyethylamine, bis-(2-hydroxyethyl)-amine or tri-(2-hydroxyethyl) -amine, eyeloaIkylamines such as bicyclohexylamine, or with procaine, dibenzylpiperidine, N-benzyl-β-phenethylamine, dehydroabietylamine, N,N'-bisdehydroabietylamine, glucamine, N-methylglucamine or bases of the pyridine type such as pyridine, collidine or quinoline.
Suitable pharmaceutically acceptable esters of carboxy groups are in-vivo hydrolysable esters.
Examples of suitable pharmaceutically acceptable in vivo hydrolysable ester groups include those which break down readily in the human body to leave the parent acid or its salt. Suitable ester groups of this type include those of part formula (i), (ii) and (iii):
-CO2CH2ORf (iii)
wherein
Ra is hydrogen, methyl, or phenyl,
Rb is C1-6 alkyl, C1-6 alkoxy or phenyl; or
Ra and Rb together form a 1,2-phenylene group optionally substituted by one or two methoxy groups; Rc represents C1-6 alkylene optionally substituted with a methyl or ethyl group - Rd and Re independently represent C1-6 alkyl; Rf represents C1-6 alkyl.
Examples of suitable in vivo hydrolysable ester group include for example acyloxyalkyl groups such as acetoxymethyl, pivaloyloxy-methyl, α-acetoxyethyl and α-pivaloyloxyethyl groups; alkoxycarbonyloxyalkyl groups, such as ethoxycarbonyl-oxymethyl and α-ethoxycarbonyloxyethyl; dialkylamino-alkyl especially di-loweralkylamino alkyl groups such as dimethylaminomethyl, dimethylaminoethyl, diethyl-aminomethyl or diethylaminoethyl and lactone groups such as phthalidyl and dimethoxyphthalidyl.
Suitable acid addition salts of compound (I) or (II),when comprising an amino group, include pharmaceutically acceptable inorganic salts such as the sulphate, nitrate, phosphate, borate, hydrochloride and hydrobromide and pharmaceutically acceptable organic acid addition salts such as acetate, tartrate, maleate, citrate, succinate, benzoate, ascorbate, methane-sulphonate, α-keto glutarate, α-glycerophosphate, and glucose-1-phosphate. Preferably the acid addition salt is a hemisuccinate, hydrochloride, α-ketoglutarate, α-glycerophosphate or glucose-1-phosphate, in particular the hydrochloride salt.
Suitable pharmaceutically acceptable amides are amides of formula CO.NRSRt wherein Rs and Rt each independently represent hydrogen or C1-6 alkyl or Rs
and Rt together with the nitrogen atom to which they are attached form a 5- or 6- membered ring.
The present invention also provides a process for the preparation of compounds of formula (II), or a pharmaceutically acceptable salt, ester or amide thereof, which process comprises cyclising a compound of formula (III):
wherein R4, R5, R6 and m are as defined in relation to formula (II); and thereafter if necessary carrying out one or more of the following steps:
(i) converting a compound of formula (II) into another compound of formula (II);
(ii) converting a compound of formula (II) into a pharmaceutically acceptable salt, ester or amide thereof.
Suitably, the cyclisation of the compound of formula (II) is carried out in the presence of a dehydrating agent, such as phosphoryl chloride.
The compounds of formula (I) may be prepared by an analogous process to that used to prepare compounds of formula (II).
The abovementioned reaction is suitably carried out in toluene, or any other suitable solvent, at any convenient temperature, preferably at an elevated
temperature such as the refluxing temperature of the chosen solvent.
The compounds of formula (III) are either known compounds or may be prepared using processes analogous to those used to prepare known compounds, for example by using the processes disclosed in Japanese Published Application No. 51111. The methods disclosed therein may also be used to prepare compounds of formula (I) or (II).
The present invention further provides a compound of the general formula (II), or pharmaceutically acceptable salt, ester or amide thereof, for use in the treatment of hyperglycaemia in human or non-human mammals.
A compound of the general formula (I) or (II), or a pharmaceutically acceptable salt thereof, may be administered per se or, preferably, as a pharmaceutical composition also comprising a pharmaceutically acceptable carrier.
In a further aspect of the present invention there is provided a pharmaceutical composition comprising a compound of the general formula (II), or a pharmaceutically acceptable salt, ester or amide thereof, and a pharmaceutically acceptable carrier therefor.
As used herein the term ''pharmaceutically acceptable'' embraces compounds, compositions and ingredients for both human and veterinary uses for example the term ''pharmaceutically acceptable salt'' embraces a veterinarily acceptable salt.
The composition may, if desired, be in the form of a pack accompanied by written or printed instructions for use.
The administration to the human or non-human mammal may be by way of oral administration or parenteral administration.
Preferably, the compound of formula (I) or (II) (hereinafter called ''the drug'') is administered in the form of a unit-dose composition, such as a unit dose oral or parenteral composition. Such unit doses will normally comprise 0.1 to 1000 mg of the drug, more usually 0.1 to 550 mg.
Such compositions are prepared by admixture and are suitably adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions. Orally administrable compositions are preferred, in particular shaped oral compositions, since they are more convenient for general use.
Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents. The tablets may be coated according to well known methods in the art.
Suitable fillers for use include cellulose, mannitol, lactose and other similar agents. Suitable
disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycollate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
These solid oral compositions may be prepared by conventional methods of blending, filling, tabletting or the like. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
For parenteral administration, fluid unit dose forms are prepared containing the drug and a sterile vehicle. The compound, depending on the vehicle and the concentration, can be either suspended or dissolved. Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling into the vial and the water removed under vacuum.
Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
In treating hyperglycaemic humans the drug may be taken in doses, such as those described above, one to six times a day in a manner such that the total daily dose for a 70 kg adult will generally be about 0.1 to 6000 mg, and more usually about 1 to 1500 mg.
In treating hyperglycaemic in mammals, especially dogs, the drug may be administered by mouth, usually once or twice a day and at about 0.025 mg/kg to 25 mg/kg, for example 0.1 mg/kg to 20 mg/kg.
The following physiological data and Examples illustrate the invention, but do not limit it in any way.
EXAMPLE 1
Methyl 2-(4-chlorophenyl)-5-methyl-4-oxazolyl-acetate
To a solution of methyl 3-(4-chlorobenzamido)-4-oxopentanoate (6.5 g) in toluene (100 ml) was added phosphoryl chloride (5 ml) and the mixture was boiled under reflux with vigorous stirring with exclusion of moisture for 5 hours. The solvent was evaporated, the residue dissolved in dichloromethane (100 ml), washed successively with saturated sodium carbonate solution (2 x 100 ml) and saturated brine (100 ml), dried (MgSO4) and evaporated. The oil thus obtained was purified by chromatography on silica gel in 1% methanol-dichloromethane to give the title compound, m.p. 59-60°C (hexane-diethyl ether).
1H nmr δ (CDCl3)
2.38 (3H,s), 3.56 (2H,s); 3.75 (3H,s); 7.4 (2H,d); 7.9 (2H,d).
EXAMPLE 2
Methyl 2-(4-chlorophenyl)-5-phenyl-4-oxazolyl-acetate
The title compound, mp. 112-113°C, was prepared from methyl 3-(4-chlorobenzamido)-3-benzoylpropionate in a similar manner to that described in Example 1.
1H nmr δ(CDCl3)
3.75 (3H,s); 3.85 (2H,s); 7.2-7.8 (7H, complex); 8.05 (2H,d).
EXAMPLE 3
Methyl 2-(4-chlorophenyl)-5-n-propyl-4-oxazolyl-acetate
The title compound, mp. 73-74°C (ether-hexane) was prepared from methyl 3-(4-chlorobenzamido)-4-oxoheptanoate in a similar manner to that described in Example 1.
1H nmr δ(CDCl3)
1.0 (3H,t); 1.4-1.9 (2H,m); 2.65 (2H,t); 3.55 (2H,s); 3.85 (3H,s); 7.4 (2H,d); 7.95 (2H,d).
EXAMPLE 4
Methyl [3-(2-(4-chlorophenyl)-5-methyl-4-oxazolyl]propionate
The title compound, mp. 66-67°C (hexane) was prepared from methyl-4-(4-chlorobenzamido)-5-oxohexanoate in a similar manner to that described in Example 1.
1H nmr δ(CDCl3)
2.30 (3H,s); 2.75 (4H, complex); 3.65 (3H,s); 7.35 (2H,d); 7.9 (2H,d).
EXAMPLE 5
Methyl [3-(2-(4-chlorophenyl)-5-ethyl-4-oxazolyl]propionate
The title compound, mp. 42-45°C (hexane), was prepared from methyl-4-(4-chlorobenzamido)-5-oxoheptanoate in a similar manner to that described in Example 1.
1H nmr δ (CDCl3)
1.25 (3H,t); 2.55-2.9 (6H, complex); 3.65 (3H,s); 7.4 (2H, d); 7.85 (2H,d).
EXAMPLE 6
Methyl [3-(2-(2,4-dichlorophenyl)-5-methyl-4-oxazolyl] propionate
The title compound, mp. 78-80°C (diethylether-hexane), was prepared from methyl-4-(2,4-dichlorobenzamido)-5-oxohexanoate in a similar manner to that described in Example 1.
1H nmr δ(CDCl3)
2.35 (3H,s); 2.75 (4H, complex); 3.75 (3H,s); 7.15-7.5 (2H, complex); 7.85 (2H,d).
BIOLOGICAL DATA
Diabetic Mice, Mid-day Blood Glucose Concentrations
C57Bl/KsJ diabetic (db/db) female mice, 5-6 weeks old, were housed 5 per cage and fed on a powdered rat and mouse breeders diet (H.C. Styles, Bewdley, Worcs.) for one week. At the end of this period, blood samples were obtained at mid-day for the determination of blood glucose in all mice. The animals then continued to receive the powdered diet or were given the powdered diet supplemented with the test compound. After 7 days, the blood glucose concentration at mid-day were again determined.
The results of the determination of mid-day blood glucose concentrations taken at the end of each treatment are shown below as the mean (mM). The comparable values for animals fed on the powdered diet alone are also shown as controls. Five mice (i.e. one cage of mice) were used on each treatment.
Test Dose
Compound Control Treated (mmol kg-1 of diet)
Example 1 19.9 9.6 6
Example 2 22.3 12.0 9
Example 5 21.0 6.6 6
Example 6 28.2 7.0 6
No adverse toxicological effects were indicated in the above tests.
Claims
1. A method for the treatment and/or prophylaxis of hyperglycaemia in humans or non-human mammals, which method comprises the administration of an effective, non-toxic amount of a compound of formula (I):
2. A method according to claim 1, wherein R1 represents a phenyl group.
3. A method according to claim 1 or claim 2, wherein R3 represents a phenyl group, preferably substituted with up to the two halogen atoms.
4. A method according to any one of claims 1 to 3, wherein n represents an integer of from 1 to 4, preferably 1, 2 or 3.
5. A method according to claim 1 , wherein the compound of formula (I) is selected from the list consisting of:
methyl 2-(4-chlorophenyl)-5-methyl-4-oxazolyl-acetate;
methyl 2-(4-chlorophenyl)-5-phenyl-4-oxazolyl-acetate;
methyl 2-(4-chlorophenyl)-5-n-propyl-4-oxazolylacetate;
methyl [3-(2-(4-chlorophenyl)-5-methyl-4-oxazolyl]propionate;
methyl [3-(2-(4-chlorophenyl)-5-ethyl-4-oxazolyl]-propionate; and
methyl [3-(2-(2,4-dichlorophenyl)-5-methyl-4-oxazolyl] propionate.
6. A compound of formula (II):
or a pharmaceutically acceptable salt, ester or amide thereof, wherein R4 represents a C1-6 alkyl, C1-6 arylalkyl or aryl group;
R5 represents a hydrogen atom or a C1-6 alkyl group;
R6 represents a substituted or unsubstituted aryl group; and m represents an integer of from 1 to 6; providing that when R4 represents lower alkyl, R5 represents a hydrogen atom or lower alkyl and m represents 1; then R6 does not represent a phenyl group or a phenyl group substituted with a halogen atom.
7. A compound according to claim 6, wherein R4 represents a phenyl group.
8. A compound according to claim 6 or claim 7, wherein R6 represents 4-chlorophenyl or
2,4-dichlorophenyl.
9. A compound according to any one of claims 6 to
8, wherein R4 represents methyl, ethyl, n-propyl or phenyl.
10. A compound according to any one of claims 6 to
9, wherein R5 represents methyl.
11. A compound according to claim 6, selected from the list consisting of:
methyl 2-(4-chlorophenyl)-5-methyl-4-oxazolyl-acetate;
methyl 2-(4-chlorophenyl)-5-phenyl-4-oxazolyl-acetate;
methyl 2-(4-chlorophenyl)-5-n-propyl-4-oxazolyl- acetate; methyl [3-(2-(4-chlorophenyl)-5-methyl-4-oxazolyl]-propionate;
methyl [3-(2-(4-chlorophenyl)-5-ethyl-4-oxazolyl]-propionate; and
methyl [3-(2-(2,4-dichlorophenyl)-5-methyl-4-oxazolyl] propionate.
12. A process for the preparation of a compound of formula (II), which process comprises cyclising a compound of formula (III):
wherein R4, R5, R6 and m are as defined in relation to formula (II); and thereafter if necessary carrying out one or more of the following steps:
(i) converting a compound of formula (II) into another compound of formula (II);
(ii) converting a compound of formula (II) into a pharmaceutically acceptable salt, ester or amide thereof.
13. A pharmaceutical composition comprising a compound of the general formula (II) and a pharmaceutically acceptable carrier therefor.
14. A compound of the general formula (II), or pharmaceutically acceptable salt thereof, for use in the treatment of hyperglycaemia in human or non-human mammals.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8531608 | 1985-12-23 | ||
GB858531608A GB8531608D0 (en) | 1985-12-23 | 1985-12-23 | Treatment |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1987003807A1 true WO1987003807A1 (en) | 1987-07-02 |
Family
ID=10590166
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1986/000789 WO1987003807A1 (en) | 1985-12-23 | 1986-12-22 | Oxazole derivatives and their use as anti-hyperglycaemic |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0250528A1 (en) |
GB (1) | GB8531608D0 (en) |
WO (1) | WO1987003807A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6156748A (en) * | 1996-10-07 | 2000-12-05 | Eli Lilly And Company | Compounds useful as neuro-protective agents |
WO2002083111A2 (en) * | 2001-04-16 | 2002-10-24 | Tanabe Seiyaku Co., Ltd. | Imidazole, thiazole and oxazole derivatives and their use for the manufacture of a medicament for the treatment and/or prevention of pollakiuria or urinary incontinence |
US6472387B1 (en) | 1996-10-07 | 2002-10-29 | Eli Lilly And Company | Methods of using compounds as neuro-protective agents |
US6767864B2 (en) | 2000-06-13 | 2004-07-27 | Bayer Cropscience Ag | Heteroaryl-substituted heterocycles |
US7420062B2 (en) | 2003-07-14 | 2008-09-02 | Bayer Cropscience, Ag | Hetaryl-substituted pyrazolidindione derivatives with pesticidal characteristics |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0092239A2 (en) * | 1982-04-19 | 1983-10-26 | Takeda Chemical Industries, Ltd. | Oxazole derivatives, production and use thereof |
EP0094612A2 (en) * | 1982-05-19 | 1983-11-23 | Tanabe Seiyaku Co., Ltd. | Novel alkyloxazolylacetic acid derivative, processes for preparation and pharmaceutical compositions containing same |
EP0096890A2 (en) * | 1982-06-15 | 1983-12-28 | Takeda Chemical Industries, Ltd. | Oxazoleacetic acid derivatives, process for their production and compositions containing said derivatives |
-
1985
- 1985-12-23 GB GB858531608A patent/GB8531608D0/en active Pending
-
1986
- 1986-12-22 WO PCT/GB1986/000789 patent/WO1987003807A1/en unknown
- 1986-12-22 EP EP19870900228 patent/EP0250528A1/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0092239A2 (en) * | 1982-04-19 | 1983-10-26 | Takeda Chemical Industries, Ltd. | Oxazole derivatives, production and use thereof |
EP0094612A2 (en) * | 1982-05-19 | 1983-11-23 | Tanabe Seiyaku Co., Ltd. | Novel alkyloxazolylacetic acid derivative, processes for preparation and pharmaceutical compositions containing same |
EP0096890A2 (en) * | 1982-06-15 | 1983-12-28 | Takeda Chemical Industries, Ltd. | Oxazoleacetic acid derivatives, process for their production and compositions containing said derivatives |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6579871B2 (en) | 1996-10-07 | 2003-06-17 | Eli Lilly And Company | Methods of using novel compounds as neuro-protective agents |
US6166216A (en) * | 1996-10-07 | 2000-12-26 | Eli Lilly And Company | Compounds useful as neuro-protective agents |
US6380213B1 (en) | 1996-10-07 | 2002-04-30 | Eli Lilly And Company | Compounds useful as neuro-protective agents |
US6423709B1 (en) | 1996-10-07 | 2002-07-23 | Eli Lilly And Company | Methods of using novel compounds as neuro-protective agents |
US6472387B1 (en) | 1996-10-07 | 2002-10-29 | Eli Lilly And Company | Methods of using compounds as neuro-protective agents |
US6156748A (en) * | 1996-10-07 | 2000-12-05 | Eli Lilly And Company | Compounds useful as neuro-protective agents |
US6767864B2 (en) | 2000-06-13 | 2004-07-27 | Bayer Cropscience Ag | Heteroaryl-substituted heterocycles |
US7141533B2 (en) | 2000-06-13 | 2006-11-28 | Bayer Cropscience Ag | Hetaryl-substituted heterocycles |
WO2002083111A2 (en) * | 2001-04-16 | 2002-10-24 | Tanabe Seiyaku Co., Ltd. | Imidazole, thiazole and oxazole derivatives and their use for the manufacture of a medicament for the treatment and/or prevention of pollakiuria or urinary incontinence |
WO2002083111A3 (en) * | 2001-04-16 | 2004-04-15 | Tanabe Seiyaku Co | Imidazole, thiazole and oxazole derivatives and their use for the manufacture of a medicament for the treatment and/or prevention of pollakiuria or urinary incontinence |
KR100863659B1 (en) * | 2001-04-16 | 2008-10-15 | 미쓰비시 타나베 파마 코퍼레이션 | Nitrogen-Containing Heterocyclic Compound and Pharmaceutical Composition Thereof |
US7759373B2 (en) | 2001-04-16 | 2010-07-20 | Mitsubishi Tanabe Pharma Corporation | Large conductance calcium-activated K channel opener |
US7420062B2 (en) | 2003-07-14 | 2008-09-02 | Bayer Cropscience, Ag | Hetaryl-substituted pyrazolidindione derivatives with pesticidal characteristics |
Also Published As
Publication number | Publication date |
---|---|
EP0250528A1 (en) | 1988-01-07 |
GB8531608D0 (en) | 1986-02-05 |
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