CA2171934C

CA2171934C - Endothelin receptor antagonists

Info

Publication number: CA2171934C
Application number: CA002171934A
Authority: CA
Inventors: Mathias Osswald; Werner Mederski; Dieter Dorsch; Claudia Wilm; Claus Schmitges; Maria Christadler
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 1995-03-18
Filing date: 1996-03-15
Publication date: 2007-04-24
Anticipated expiration: 2016-03-15
Also published as: ZA962144B; EP0733626B1; KR100424045B1; GR3029893T3; HUP9600663A3; JPH08269027A; DK0733626T3; DE19509950A1; TR199600212A2; CO4700473A1; NO305907B1; RU2168503C2; BR9601028A; PL184332B1; HU9600663D0; SK280926B6; CA2171934A1; SK36396A3; US5726194A; AU4803996A

Abstract

Novel compounds of the formula I

(see formula I) in which R1 , R2 , R3 , -A=B-C=D- , Ar and X have the meaning indicated in claim 1, and their salts show endothelin receptor-antagonistic properties.

Description

- I -Endothelin receptor antagonists The inven~ion relates to compounds of the formula I
Ar-S02 NH
~, N
R a X
~i R ~p R3 N
in which -A=B-C=D- is a -CH=CH-CH=CH- group in which 1 or 2 CH groups can also be replaced by N, Ar is Ph or naphthyl, which is unsub-stituted or mono-, di-~ or trisubstituted by H, Hal, Q, alkenyl having up to 6 C
atoms, Ph, OPh, NO2, NR4R5, NHCOR4, CF3, OCF3 , CN , OR4 , COOR4 , ( CH2 ) nCOOR4 , ( CH2 ) ~,NR4R5 , -N=C=O or NHCONR4R5 , R1, R2 and R3 in each case independently of one another are absent , H, Hal , Q, CF3 , NOZ , NR4R~, CN, COOR4 or NHCOR4, R~ and RS in each case independently of one another are H or Q, or together are also -CH2- (CHz) n-CHz_, Q is alkyl having 1 to 6 C atoms, Ph is phenyl, X is O or S, Hal is F, C1, Br or I, n is 1, 2 or 3, and also their salts, excluding 4-methyl-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-methyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-amino-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide and 4-amino-N-(2,1,3-benzothiadiazol-5yl)benzenesulfonamide.
According to another aspect of the present invention, there is provided the following preferred salts:
5-bromo-2-ethyl-N-(2,1,3-benzothiadiazol-5-yl)benzene sulfonamide 2,5-dichloro-N-(2,1,3-benzothiadiazol-5-yl)benzene sulfonamide 5-bromo-2-propyl-N-(2,1,3-benzothiadiazol-5-yl)benzene sulfonamide 5-dimethylamino-N-(2,1,3-benzothiadiazol-5-yl)naphthalene-sulfonamide 5-dimethylamino-N-[6-methyl-(2,1,3-benzothiadiazol-5-yl)]naphthalenesulfonamide 5-dimenthylamino-N-[4-bromo-(2,1,3-benzothiadiazol-5-yl)]naphthalenesulfonamide 2a 5-dimethylamino-N-(2,1,3-benzothiadiazol-4-yl)naphthalene-sulfonamide 5-dimethylamino-N-(1,2,5-oxadiazole-[3,4-b]pyridin-6-yl)-naphthalenesulfonamide 5-dimethylamino-N-(1,2,5-benzoxadiazol-5-yl)-1-naphthalenesulfonamide 5-dimethylamino-N-(6-bromo-7-methyl-1,2,5-benzoxadiazol-5-yl)-1-naphthalenesulfonamide 2-phenyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide.
Compounds of formula I display endothelin receptor antagonist properties.
Similar compounds are disclosed in EP 0 558 258 Al, EP 0 569 193 A1 and WO 94/27979.
4-Methyl-N-(2,1,3-benzothiadiazol-5-yl)benzene-sulfonamide is described in Khim. Geterotsikl. Soedin.
(1968), 5, 812-14, 4-nitro-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide and 4-amino-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide are described in Zh. Obshch. Khim.
(1954), 24, 133-136.
No pharamcological actions are described, however, for these compounds.
The invention was based on the object of finding novel compounds having useful properties, in particular those which can be used for the production of medicaments.
It has been found that the compounds of the formula I and their salts have very useful pharamcological properties together with good tolerability. In particular, they show endothelin receptor-antagonistic ~ ~ l 1 X34 properties and can therefore be employed for the treat-ment of illnesses such as hypertension, cardiac in-sufficiency, coronary heart disease, renal, cerebral and myocardial ischaemia, renal insufficiency, cerebral infarct, subarachnoid haemorrhage, arteriosclerosis, pulmonary high blood pressure, inflammations, asthma, prostate hyperplasia, endotoxic shock and in the case of complications after the administration of substances such as cyclosporin, and also other illnesses associated with endothelin activities.
The compounds show, inter alia, a high affinity for the endothelin subreceptors ETA and ETB. These actions can be determined according to customary in vitro or in vivo methods, such as described by P.D. Stein et al., J. Med. Chem. ~, 1994, 329-331 and E. Ohlstein et al., Proc. Natl. Acad. Sci. USA
1994, 8052-8056.
The hypotensive action is described by M.K. Bazil et al., J. Cardiovasc. Pharmacol. ~, 1993, 897-905 and J. Lange et al., Lab Animal ~Q, 1991, Appl.
Note 1016.
The compounds of the formula I can be employed as pharmaceutical active compounds in human and veteri-nary medicine, in particular for the prophylaxis and/or therapy of cardiac, circulatory and vascular disorders, especially hypertension and cardiac insufficiency.
The invention relates to the compounds of the formula I and their salts, and to a process for the preparation of these compaunds and their salts, charac terized in that (a) a compound of the formula II

~A
8'\ iN\
R~~
C/' wN
D

in which -A=B-C=D-, R1., R2, R3 and X have the meanings indicated previously herein is reacted with a compound of the formula III
Ar-SOZ-E III
in which E is C1, Br, I or a free or reactive functionally mod ified OH group and Ar has the meaning indicated previously herein or (b) in that for the preparation of a compound of the formula I, in which X is S and of 4-methyl-N-(2,1,3-benzo-thiadiazol-5-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-S-yl)benzene-sulfonamide or 4-amino-N-(7,1,3-benzo-t~iadiazol-5-yl)benzenesulfonamide, a compound of the formula IV
R2 R3 Hz ~--SG2 N
A Nt-~
R ~-+- I
C/ ' D N
in which -A=B-C=D-, Ar, R1, RZ and R3 have the meanings indicated previously herein is reacted with thionyl chloride or a reactive derivative of this compound, or c) in that for the preparation of a compound of the formula I
in which X is O
a compound of the formula V

Ar-Sp~-N
A
~ N\
R'+ ° V
C,( ~ N.
~2/~ D R3 O
in which -A=~-C=D-, Ar, R1, R2 and R3 have the meanings lTldicaf:ed previously herein is reduced, and/or in that in a compound of the formula I
one or more radicals Rl, R2 and/or R3 is con-verted into one or more other radicals Rl, R2 and/or R3, by _ .
i) reducing a nitro group to an amino group, ii) replacing a bromo substituent by a cyano group, iii) hydrolysing a cyano group to a carboxyl group, iv) esterifying a carboxyl group, v) converting an amino group by reductive amination into an alkylated amine or CA 02171934 1996-04-10 L ~ ~ ~ 9 ~ 4 vi) acylating an amino group and/or converting a base or acid of the formula I into one of its salts.
Above and below, the radicals or parameters -A=B-C=D-, Ar, R1 to R5, Q, Ph, X, Hal and n have the meanings indicated under the formulae I to V, if noth-ing is expressly stated otherwise.
In the above formulae, Q has 1 to 6, preferably 1, 2, 3 or 4 C atoms. Q is preferably methyl, further-more ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, and further also pentyl, 1-, 2- or 3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-, 2-, 3- or 4-methylpentyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or 3,3-dimethylbutyl, f-or 2-ethylbutyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, or 1,1,2- or 1,2,2-trimethylpropyl.
Alkenyl is preferably vinyl, 1- or 2-propenyl, 1-butenyl, and further 1-pentenyl or 1-hexenyl.
Hal is preferably F, Cl or Br, but also I.
Ar is unsubstituted, preferably - as indicated - monosubstituted phenyl or naphthyl, specifically preferably phenyl, o- or m-tolyl, o-, m- or p-ethyl-phenyl, o-, m- or p-propylphenyl, o-, m- or p-isopropylphenyl, o-, m- or p-tent-butylphenyl, o-, m- or p-trifluoromethylphenyl, o-, m- or p-phenylphenyl, o-, m- or p-hydroxyphenyl, o- or m-nitrophenyl, o- or m-aminophenyl, o-, m- or p-methylaminophenyl, o-, m- or p-dimethylaminophenyl, o-, m- or p-acetamidophenyl, o-, m- or p-(trifluoromethoxy)phenyl, o-, m- or p-cyanophenyl, _, . .__._._.__. ~..,...~."~...-...._. _ ._..___..__.....~........__..~.,~.....~.~_~_ _8_ o-, m- or p-(N-pyrrolidino)phenyl, o-, m- or p-(N-piperidino)phenyl, o-, m- or p-methoxyphenyl, o-, m- or p-ethoxyphenyl, o-, m- or p-phenoxyphenyl, o-, m-or p-carboxyphenyl, o-, m- or p-methoxycarbonylphenyl, 0-, m- or p-ethoxycarbonylphenyl, o-, m- or p-(carboxy-methyl)phenyl, o-, m- or p-(methoxycarbonylmethyl)-phenyl, o-,, m- or p-(methoxycarbonylethyl)phenyl, o-, m- or p-(aminomethyl)phenyl, o-, m- or p-(N-methyl-aminomethyl)phenyl, o-, m- or p-(N,N-dimethylamino)-phenyl, o-, m- or. p-(N-ethylamino)phenyl, o-, m- or p-(N,N-diethylamino)phenyl, o-, m- or p-(N,N-dimethyl-aminomethyl)phenyl, o-, m- or p-(N-pyrrolidinomethyl)-phenyl, o-, m- or p-(N-piperidinomethyl)phenyl, o-, m-or p-isocyanatophenyl, o-, m- or p-carbamidophenyl, o-, m- or p-(N-methylcarbamoyl)phenyl, o-, m- or p-(N,N-dimethylcarbamoyl)phenyl, o-, m- or p-fluoro-phenyl, o-, m- or p-bromophenyl, o-, m- or p-chloro-phenyl, further preferably naphthyl, 5-methylnaphthyl, 5-ethylnaphthyl, 5-propylnaphthyl, 5-isopropylnaphthyl, 5-tert-butylnaphthyl, 5-trifluoromethylnaphthyl, 5-phenylnaphthyl, 5-hydroxynaphthyl, 5-nitronaphthyl, 5-aminonaphthyl, 5-N-methylaminonaphthyl, 5-N,N-di-methylaminonaphthyl, 5-acetamidonaphthyl, 5-(trifluoro-methoxy)naphthyl, 5-cyanonaphthyl, 5-(N-pyrrolidino)-naphthyl, 5-(N-piperidino)naphthyl, 5-methoxynaphthyl, 5-ethoxynaphthyl, 5-carboxynaphthyl, 5-methoxycarbonyl-naphthyl, 5-ethoxycarbonylnaphthyl, 5-(carboxymethyl)-naphthyl, 5-(methoxycarbonylmethyl)naphthyl, 5-(ethoxy-carbonylmethyl)naphthyl, 5-(aminomethyl)naphthyl, 5-(N-methylaminomethyl) naphthyl, 5-(N,N-dimethylamino-methyl)naphthyl, 5-N-ethylaminonaphthyl, 5-(N,N-diethylamino)naphthyl, 5-(N-pyrrolidinomethyl)naphthyl, _ g _ 5-(N-piperidinomethyl) naphthyl, 5-isocyanatonaphthyl, 5-carbamidonaphthyl, 5-(N-methylcarbamoyl)naphthyl, 5-(N,N-dimethylcarbamoyl)naphthyl, 5-N-isopropylamino-naphthyl, 5-N-isopropyl-N-methylaminonaphthyl, 5-fluoronaphthyl, 5-chloronaphthyl, 5-bromonaphthyl, further preferably 2,3-, 2,4-, 2,5-, 2,6~-, 3,4- or 3,5-difluorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dichlorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dibromophenyl, 2-chloro-3-methyl, 2-chloro-4-methyl, 2-chloro-5-methyl, 2-chloro-6-methyl, 2-methyl-3-chloro, 2-methyl-4-chloro, 2-methyl-5-chloro, 2-methyl-6-chloro, 3-chloro-4-methyl, 3-chloro-5-methyl or 3-methyl-4-chlorophenyl, 2-bromo-3-methyl, 2-bromo-4-methyl, 2-bromo-5-methyl, 2-bromo-6-methyl, 2-methyl-3-bromo, 2-methyl-4-bromo, 2-methyl-5-bromo, 2-methyl-6-bromo, 3-bromo-4-methyl, 3-bromo-5-methyl or 3-methyl-4-bromophenyl, 2,4- or 2,5-dinitrophenyl, 2,5- or 3,4-dimethoxyphenyl, 3-nitro-4-chlorophenyl, 2-amino-3-chloro, 2-amino-4-chloro, 2-amino-5-chloro or 2-amino-6-chlorophenyl, 2-nitro-4-N,N-dimethylamino or 3-nitro-4-N,N-dimethylaminophenyl, 3-carboxy-2-methoxy, 3-carboxy-4-methoxy or 3-carboxy-5-methoxyphenyl, 2,3,4-, 2,3,5-, 2,3,6-, 2,4,6- or 3,4,5-trichloro-phenyl, 2,4,6-tri-tert-butylphenyl, further preferably 2-nitro-4-(trifluoromethyl)phenyl, 3,5-di-(trifluoro-methyl)phenyl, 2,5-dimethylphenyl, 2-hydroxy-3,5-dichlorophenyl, 2-fluoro-5- or 4-fluoro-3-(trifluoro-methyl)phenyl, 4-chloro-2- or 4-chloro-3-(trifluoro-methyl), 2-chloro-4- or 2-chloro-5-(trifluoromethyl)-phenyl, 4-bromo-2- or 4-bromo-3-(trifluoromethyl)-phenyl, p-iodophenyl, p-vinylphenyl, 5-(N,N-dibutyl-amino)naphthyl, 2-nitro-4-methoxyphenyl, 2,5-dimethoxy-..__ .....~...... _..._._ . ..___.... ..~_...._.._ _..._._..-. ~.~ ,.~.-",.~",~~,~,- .m.~... . ..

4-nitrophenyl, 3,5-dicarboxyphenyl, 2-chloro-3-nitro-5-carbox-yphenyl, 4-chloro-3-carboxyphenyl, 2-methyl-5-nitrop'?enyl, 2,4-dimethyl-3-nitrophenyl, 3 ,6-dichloro-4-aminophenyl, 4-fluoro-3-chlorophenyl, 4 -fluoro-3,5-dimethylphenyl, 2-fluoro-4-bromophenyl, 2,5 -difluoro-4-bromopzenyl, 2,4-dichloro-.5-methylphenyl, 3-bromo-6-methoxyphenyl, 3-chloro-6-methoxyphenyl, 3-chloro-4-acetamidophenyl, 4-hydroxy-3-carboxyphenyl, 2-methoxy-5-methylphenyl or 2,4,6-triisopropylphenyl.

The radical -A=B-C=D- is preferably -CH=CH-CH=N-, and further -CH=N-CH=CH- or -CH=N-CH=N-, but particularly preferably -CH=CH-CH=CH-.

The radicals R~, R2 and R3 are in each case independently of one another preferably H, Q, in par-L5 ocular CH3, Hal, in particular chlorine or bromine, but further also preferably N02 or CF3.

The parameter n is preferably 0 or 1, and further preferably 2.

The compounds of the formula I can have one or more chiral centres and therefore occur in various stereoisomeric forms. The formula I includes all these forms.

Accordingly, the invention relates in particular to those compounds of the formula I in which at least one of the radicals mentioned has one of the preferred meanings indicated above. Some preferred groups of compounds can be expressed by the following subformulae Ia to Ig which correspond to the formula I
and in which the radicals which are not described in greater detail have the meaning indicated under the formula I, but in which in Ia X is S;

,~.. ~ 1719 3 4 in ~b X is O;

in .c X is S and -A=B-C=D- is -CH=CH-CH=CH-;

in .d X is O and -A=B-C=D- is -CH=CH-CH=CH--;

in _e X is O and -A=B-C=D- is -CH=CH-CH=N-;

in If X is S, -A=B-C=D- is -CH=CH-CH=CH-, R1 is H, RZ is Hal and R3 is methyl;

in Ig Ar is 5-(N,N-dimethylamino)naphthyl.

The compounds of the formula I and also the starting substances for their preparation are otherwise prepared by methods known per se, as are described in the literature (e.g. in the standard works such as Houben-Weyl, Methoden der organischen Chemie (Methods of Organic Chemistry), Georg-Thieme-Verlag, Stuttgart;
but in particular in EP 0569 193 A and WO 94/27979), namely under reaction conditions which are known and LO suitable for the reactions mentioned. In this case use can also be made of variants which are known per se but not mentioned here in greater detail.
The starting substances can, if desired, also be formed in situ, such that they are not isolated from the reaction mixture, but immediately reacted further to give the compounds of the formula I.
The compounds of the formula I can preferably be obtained by reacting compounds of the formula II
with compounds of the formula III.

CA 02171934 1996-04-10 G ~ 7 1 9 3 4 In the compounds of the formula III, E is preferably Cl, Br, I or a reactive modified OH group such as alkylsulfonyloxy having 1-6 C a~.oms (preferably methylsulfonyloxy) or arylsulfonyloxy having 6-10 C
atoms (preferably phenyl- or p-tolylsulfonyloxy).
The reaction is performed, as a rule, in an inert solvent in the presence of one or more bases, preferably of a tertiary amine, e.g. triethylamine, pyridine, 4-dimethylaminopyridine, expediently at tem-peratures between 0 and 150°, preferably between 40 and 90° . An excess of the amine can also be used as a sol-vent.
Suitable inert solvents are, for example, hydrocarbons such as hexane, petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons such as trichloroethylene, 1,2-dichloroethane, carbon tetra-crloride, chloroform or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; glycol ethers such as ethylene glycol mono-methyl or monoethyl ether (methyl glycol or ethyl glycol), ethylene glycol dimethyl ether (diglyme);
ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide or dimethylformamide (DMF); nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); carbon disulfide;
carboxylic acids such as formic acid or acetic acid;
nitro compounds such as nitromethane or nitrobenzene;
:30 esters such as ethyl acetate or mixtures of the sol-vents mentioned.

The starting compounds of the formula II are generally novel. However, they can be prepared by methods which are knocon per se. For example, 5-amino-6-methyl-2,1,3-benzot.hiadiazole can thus be prepared from 5-nitro-6-methyl-2,1,3-benzothiadiazole by hydro-genation on Raney NickelTMin an inert solvent such a methanol. This is expediently carried out at tempera-tures between 0 and approximately 200°; preferably between 30 and 80°.
l0 Compounds of the formula I in which X is S can furthermore be obtained by reacting compounds of the formula IV, which. are generally novel, with thionyl chloride or a~ reactive derivative. of this compound such as thionylaniline, analogously to known processes, as are described in the literature (e. g. J. Heterocycl.
Chem. 7, 629 (1970)), in an inert solvent in the presence of one or more bases, preferably of a tertiary amine, e.g. triethylamine, pyridine, 4-dimethylaminopyridine, expediently at temperatures 2U between 0 and 150°, preferably between 40 and 90°. An excess of the amine can also be used as a solvent.
Compounds of the formula I in which X is O can furthermore be obtained by reacting compounds of the Lormula V, which are generally novel, with reducing compounds such as C1-SOz-N=C=O, POC13, PC13, Na2Sz0q, Ph,P
or P(OCzHs)3 analogously to known processes, as are described in the literature (e. g. Tetrahedron ~, 5209 (1988), Tetrahedron ~$, 8199 (1992), Z. Chem. ~, 257 (1980), J. Org. Chem. ~, 1774 (1982), J. Org. Chem.
~, 1656 (1963) or J. Med. Chem. ~" 305 (1968)).
The starting compounds of the formula V can be prepared by methods which are known per se. For '171934 example, 4-tert-butyl-N-(2,1,3-benzoxadiazole-1-N-oxid-5-yl)benzenesulfonamide can thus be prepared from 4-pert-butyl-N-(4-chloro-3-nitro)benzenesulfonamide by reaction with sodium azide under phase-transfer catalysis via 4-tert-butyl-N-(4-azido-3-nitro)benzene-sulfonamide and subsequent cyclization in glacial acetic acid.
It is further possible to convert a compound of the formula I into another compound of the formula I by converting one or more radicals R1, R2 and/or R3 into one or more other radicals R1, R2 and/or R3, e.g. by reducing nitro groups, for example by hydrogenation on Raney Nickel or Pd-carbon in an inert solvent such as methanol or ethanol, to amino groups and/or converting bromo substituents by reaction with, for example, copper (I) cyanide into cyano groups and/or hydrolysing cyano groups to COON groups and/or esterifying carboxyl groups by reaction with alcohols and/or alkylating nitro groups under hydrogenolytic con-ditions, alkylated amines being obtained.
Free amino groups can further be acylated in a customary manner using an acid chloride or anhydride or alkylated using an unsubstituted or substituted alkyl halide, expediently in an inert solvent such as d~_chloromethane or THF and/or in the presence of a base such as triethylamine or pyridine at temperatures between -60 and +30°.
If desired, a functionally modified amino and/or hydroxyl group in a compound of the formula I
can be liberated by solvolysis or hydrogenolysis according to customary methods. For example, a compound ~.~..
~1?1934 _ 15 _ of the formula I which contains an NHCOR4 or a COOR' group can thus be converted into the corresponding compound of the formula I which, instead of this, con-tains an NH2 or a COOH group. COOR4 groups can be hydro-lysed, for example, using NaOH or KOH in water, water-THF or water-dioxane at temperatures between 0 and 100°.
A base of the formula I can be converted with an acid to the associated acid addition salt, for example by reaction of equivalent amounts of the base and of the acid in an inert solvent such as ethanol and subsequent evaporation. For this reaction, in particular, possible acids are those which yield physiologically acceptable salts. Inorganic acids can thus be used, e.g. sulfuric acid, nitric acid, halo-hydric acids such as hydrochloric acid or hydrobromic acid, phosphoric acids such as orthaphosphoric acid, sulfamic acid, and also organic acids, in parti cular aliphatic, alicyclic, araliphatic, aromatic or hetero-cyclic mono- or polybasic carboxylic, sulfonic or sul-furic acids, e.g. formic acid, acetic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, malefic acid, lactic acid, tartaric acid, malic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, iso-nicotinic acid, methane- or ethanesulfonic acid, ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naph-thalenemono- and disulfonic acids, laurylsulfuric acid.

Salts with physiologically unacceptable acids, e.g.

picrates, can be used far the isolation and/or puri-fication of the compounds of the formula I.

On the other hand, compounds of the formula I
can be conve=ted using bases (e. g. sodium or potassium hydroxide or carbonate) into the corresponding metal salts, in particular alkali metal or alkaline-earth metal salts, or into the corresponding ammonium salts.
The invention further relates to the use of the compounds of the formula I and/or 4-methyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide and/or 4-nitro-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfon-amide and/or 4-amino-N-(2,1,3-benzothiadiazol-5-yl)-benzenesulfonamide and/or their physiologically accept-able salts for the production of pharmaceutical preparations, in particular by non-chemical routes. In this context, they can be brought into a suitable dose :L5 form together with at least one solid, liquid and/or semi-liquid excipient or auxiliary and, if appropriate, in combination with one or more further active com-pounds.
The invention further relates to pharmaceutical preparations comprising at least ane compound of the formula I and/or 4-methyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide and/or 4-nitro-N-(2,1,3-benzo-thiadiazol-5-yl)benzenesulfonamide and/or 4-amino-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide and/or one of their physiologically acceptable salts.
These preparations can be esed as medicaments in human or veterinary medicine. Possible excipients are organic or inorganic substances which are suitable for enteral (e.g. oral) or parenteral administration or topical application and do not react with the novel compounds, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, ~1~1934 w _ 17 -glycerol triacetate, gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc and petro-leum jelly. In particular, tablets, pills, coated tablets, capsules, powders, granules, syrups, juices or drops are used for oral administration, suppositories are used for rectal administration, solutions, prefer-ably oily or aqueous solutions, and further suspen-sions, emulsions or implants, are used for parenteral administration and ointments, creams or powders are used for topical application. The novel compounds can also be lyophilised and the lyophilisates obtained, used, for example, for the production of injection preparations. The preparations indicated can be sterilized and/or contain auxiliaries such as lubri-cants, preservatives, stabilizers and/or wetting agents, emulsifiers, salts for affecting the osmotic pressure, buffer substances, colorants, flavourings and/or aromatic substances. They can also contain, if desired, one or more other active compounds, e.g. one or more vitamins.
The compounds of the formula I and their physiologically acceptable salts can be used in the control of disorders, in particular of hypertension and cardiac insufficiency.
In this context, the substances according to the invention are generally preferably administered in doses of between approximately 1 and 500 mg, in particular between 5 and 100 mg per dose unit. The daily dose is preferably between approximately 0.02 and 10 mg/kg of body weight. The specific dose for any patient depends, however, on all sorts of factors, for example on the activity of the specific compound ~ ~ 71934 employed, on the age, body weight, general state of health, sex, on the diet, on the time and route of administration, on the excretion rate, pharmaceutical substance combination and severity of the particular disease to which the therapy applies. Oral admini-stration is preferred.
Above and below, all temperatures are indicated in °C. In the following examples, "customary working up" means: water is added, if necessary, the mixture is adjusted, if necessary, depending on the constitution of the final product, to pHs of between 2 and 10, and extracted with ethyl acetate or dichloromethane, the solid is separated off, and the organic phase is dried over sodium sulfate, evaporated and purified by chroma-tography on silica gel and/or by crystallization. Rf values on silica gel; eluent: ethyl acetate/methanol 9:1.
~xammle 1 A solution of 3 g of 5-dimethylamino-naphthalene-sulfonylchlaride ("A") in 10 ml of pyridine is added to a solution of 1.53 g of 5-amino-2,1,3-benzothiadiazole, obtainable by hydrogenation of 5-nitro-2,1,3-benzothiadiazole on Raney Nickel in 2S methanol, in 15 ml of pyridine, and the mixture is stirred for 24 hours at 60°, then added to 75 ml of 2N
hydrochloric acid and worked up in the customary manner. 5-Dimethylamino-N-(2,1,3-benzothiadiazol-5-yl) 1-naphthalenesulfonamide is obtained as a yellow solid, m.p. 73°.
Analogously, from the following mZ-5-amino-2,1,3-benzothiadiazoles, in which mZ is _~_....__._ _......._m.~,.~.~.........-"~".~- .,.-.,"..~", ...

x:171934 4-methyl 6-methyl 7-methyl 4,6-dimethyl 4,7-dimethyl 6,7-dimethyl 4-trifluoromethyl 6-trifluoromethyl 7-trifluoromethyl 4-bromo 6-bromo 7-bromo 4,6-dibromo 4,7-dibromo 6,7-dibromo 4-bromo-6-methyl 4-bromo-7-methyl 6-bromo-7-methyl 4-methyl-6-bromo 4-methyl-7-bromo 6-methyl-7-bromo 4-bromo-6-ethyl 4-bromo-7-ethyl 6-bromo-7-ethyl 4-ethyl-6-bromo 4-ethyl-7-bromo 6-ethyl-7-bromo 4-bromo-6-trifluoromethyl 4-bromo-7-trifluoromethyl 6-bromo-7-trifluoromethyl 4-trifluoromethyl-6-bromo 4-trifluoromethyl-7-bromo ., 2~?193 - a0 -6-trifluoromethyl-7--bromo 4-chloro 6-chloro 7-chloro 4-nitro 6-nitro 7-nitro 4-bromo-6-tert-butyl 4-bromo-7-tert-butyl 6-bromo-7-tert-butyl 4-tert-butyl-6-bromo 4-tert-butyl-7-bromo 6-tert-butyl-7-bromo 4-chloro-6-methyl u5 4-chloro-7-methyl 6-chloro-7-methyl 4-methyl-6-chloro 4-methyl-7-chloro 6-methyl-7-chloro 4-dimethylamino 6-dimethylamino 7-dimethylamino 4-cyano 6-cyano :?5 7-cyano 4-methoxycarbonyl 6-methoxycarbonyl 7-methoxycarbonyl 4-ethoxycarbonyl :30 6-ethoxycarbonyl 7-ethoxycarbonyl 4-acetamido -.-__...w.-.,.~..-..-...._..._....__. ___. _- .__ ._ ~.. __ _-. . _._._.
~.~.~.,..~.~ ._......_ .... .

...~~

6-acetamido 7-acetamido with "A", the 5-dimethylamino-mZ-1-naphthalenesulfon-amides below are obtained, in which mZ is N-(4-methyl-2,1,3-benzothiadiazol-5-y1) N-(6-methyl-2,1,3-benzothiadiazol-5-yl) N-(7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(4,7-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(6,7-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyi-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-2,1,3-benzothiadiazol-5-yl), m.p. 151°
N-(6-bromo-2,1,3-benzothiadiazol-5-yl) N-(7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzothiadiazol-5-y1) N-(4,7-dibromo-2,1,3-benzothiadiazol-5-yl) N-(6,7-dibromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) z5 N-(4-methyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-ethyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) .... .~ ......._.. ......,.....~."~».~.,.~. ,.~... _. . ._..-_ . ._. _,..-..~_.___... ._.__._.. _w-___....~.._._...,_..__.

~ i 7 i 934 N-(6-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-?-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-?-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-?-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-?-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-2,1,3-benzothiadiazol-5-yl), m.p. 168°
N-(6-chloro-2,1,3-benzothiadiazol-5-yl) N-(?-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-vitro-2,1,3-benzothiadiazol-5-yl) N-(6-vitro-2,1,3-benzothiadiazol-5-yl) N-(?-vitro-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-tert-butyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-?-tert-butyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-?-tert-butyl-2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-?-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-6-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-chloro-?-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-6-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-?-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-dimethylamino-2,1,3-benzothiadiazol-5-yl) ~ 17 i 934 N-(6-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(7-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(4-cyano-2,1,3-benzothiadiazol-5-yi) N-(6-cyano-2,1,3-benzothiadiazol-5-yl) N-(7-cyano-2,1,3-benzothiadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-metho~ycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(4-acetamido-2,1,3-benzothiadiazol-5-yl) N-(6-acetamido-2,1,3-benzothiadiazol-5-yl) N-(7-acetamido-2,1,3-benzothiadiazol-5-yl).
Analogously, by reaction of 4-amino-2,1,3-benzothiadiazole with "A", 5-dimethylamino-N-(2,1,3-benzothiadiazol-4-yl)-1-naphthalene sulfonamide, m.p. 81°, is obtained and from the following 4-amino-mZ-2,1,3-benzo-thiadiazoles, in which mZ is S-methyl 6-methyl 7-methyl 5,6-dimethyl 5,7-dimethyl 6,7-dimethyl 5-trifluoromethyl 6-trifluoromethyl 7-trifluoromethyl 5-bromo 6-bromo 7-bromo 5,6-dibromo 5,7-dibromo 6,7-dibromo 5-bromo-6-methyl 5-bromo-7-methyl 6-bromo-7-methyl 5-methyl-6-bromo :LO 5-methyl-7-bromo 6-methyl-7-bromo 5-bromo-6-ethyl 5-bromo-7-ethyl 6-bromo-7-ethyl 5-ethyl-6-bromo 5-ethyl-7-bromo 6-ethyl-7-bromo 5-bromo-6-trifluoromethyl S-bromo-7-trifluoromethyl 6-bromo-7-trifluoromethyl 5-trifluoromethyl-6-bromo 5-trifluoromethyl-7-bromo 6-trifluoromethyl-'7-bromo 5-chloro 6-chloro 7-chloro 5-nitro 6-nitro 7-nitro 5-bromo-6-tert-butyl 5-bromo-7-tert-butyl 6-bromo-7-tent-butyl _.. .r._..._._._ .._._..__..,.._.~......~...,~~-..,_.~...~.. __...

~' i 71934 5-tert-butyl-5-bromo 5-tert-butyl-7-bromo 6-tert-butyl-7-bromo 5-chloro-6-methyl 5-chloro-7-methyl 6-chloro-7-methyl 5-methyl-6-chloro 5-methyl-7-chloro 6-methyl-7-chloro 5-dimethylamino 6-dimethylarnino 7-dimethylamino 5-cyano 6-cyano 7-cyano 5-methoxycarbonyl 6-methoxycarbonyl 7-methoxycarbonyl 5-ethoxycarbonyl 6-ethoxycarbonyl 7-ethoxycarbonyl 5-acetamino 5-acetamido 7-acetamido with "A", the 5-dimethylamino-mZ-1-naphthalenesulfon-amides below are obtained, in which mZ is N-(5-methyl-2,1,3-benzothiadi~zol-4-yl) N-(6-methyl-2,1,3-benzothiadiazal-4-yl) N-(7-methyl-2,1,3-benzothiadiazol-4-yl) N-(5,6-dimethyl-2,1,3-benzothiadiazol-4-yl) CA 02171934 1996-04-~ i ~ ~ 9 ~ 4 N-(5,7-dimethyl-2,1,3-benzothiadiazol-4-yl) N-(6,7-dimethyl-2,1,3-benzothiadiazol-4-yl) N-(5-trifluoromethyl-2,1,3-benzothiadiazol-4-yl) N-(6-trifluoromethyl-2,1,3-benzothiadiazol-4-yl) N-(7-trifluoromethyl-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-2,1,3-benzothiadiazol-4-yl) N-(6-bromo-2,1,3-benzothiadiazol-4-yl) N-(7-bromo-2,1,3-benzothiadiazol-4-yl) N-(5,6-dibromo-2,1,3-benzothiadiazol-~4-yl) N-(5,7-dibromo-2,1,3-benzothiadiazol-4-yl) N-(6,7-dibrorno-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-6-methyl-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-7-methyl-2,2,3-benzothiadiazol-4-yl) N-(6-bromo-7-methyl-2,1,3-benzothiadiazol-4-yl) N-(5-methyl-6-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-methyl-7-bromo-2,1,3-benzothiadiazol-4-yl) N-(6-methyl-7-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-6-ethyl-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-7-ethyl-2,1,3-benzothiadiazol-4-yl) N-(6-bromo-7-ethyl-2,1,3-benzothiadiazol-4-yl) N-(5-ethyl-6-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-ethyl-7-bromo-2,1,3-benzothiadiazol-4-yl) N-(6-ethyl-7-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-6-trifluoromethyl-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-7-trifluoromethyl-2,1,3-benzothiadiazol-4-y1 ) N-(6-bromo-7-trifluoromethyl-2,1,3-benzothiadiazol-4-yl) N-(5-trifluoromethyl-6-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-trifluo=omethyl-'7-bromo-2,1,3-benzothiadiazol-4-yl) N-(6-triflucromethyl-7-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-chloro-2,1,3-benzothiadiazol-4-yl) N-(6-chloro-2,1,3-benzothiadiazol-4-yl) N-(7-chloro-2,1,3-benzothiadiazol-4-yl) N-(5-nitro-2,1,3-benzothiadiazol-4-y1) N-(6-nitro-2,1,3-benzothiadiazol-4-yl) N-(7-nitro-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-6-tent-butyl-2,1,3-benzothiadiazol-4-yl) N-(5-bromo-7-tert-butyl-2,1,3-benzothiadiazol-4-yl) N-(6-bromo-7-tent-butyl-2,1,3-benzothiadiazol-4-yl) N-(5-tert-butyl-6-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-tert-butyl-7-bromo-2,1,3-benzothiadiazol-4-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzothiadiazol-4-yl) N-(5-chloro-5-methyl-2,1,3-benzothiadiazol-4-yl) N-(5-chloro-7-methyl-2,1,3-benzothiadiazol-4-yl) N-(6-chloro-'7-methyl-2,1,3-benzathiadiazol-4-yl) N-(5-methyl-6-chloro-2,1,3-benzothiadiazol-4-yl) N-(5-methyl-7-chloro-2,1,3-benzothiadiazol-4-yl) N-(6-methyl-7-chloro-2,1,3-benzothiadiazol-4-yl) N-(5-dimethylamino--2,1,3-benzothiadiazol-4-yl) N-(6-dimethylamino-2,1,3-benzothiadiazol-4-yl) N-(7-dimethylamino-2,1,3-benzothiadiazol-4-yl) N-(5-cyano-2,1,3-benzothiadiazol-4-yl) N-(6-cyano-2,1,3-benzothiadiazol-4-yl) N-(7-cyano-2,1,3-benzothiadiazol-4-yl) N-(5-methoxycarbonyl-2,1,3-benzothiadiazol-4-yl) N-(6-methoxycarbonyl-2,1,3-benzothiadiazol-4-yl) N-(7-methoxycarbonyl-2,1,3-benzothiadiazol-4-yl) N-(5-ethoxycarbonyl-2,1,3-benzothiadiazol-4-yl) - CA 02171934 1996-04-10 ~ ~ ? ~ 9 3 4 _ 28 _ N-(6-ethoxycarbonyl-2,1,3-benzothiadiazol-4-yl) N-(7-ethoxycarbonyl-2,1,3-benzothiadiazol-4-yl) N-(5-acetamido-2,1,3-benzothiadiazol-4-yl) N-(6-acetamido-2,1,3-benzothiadiazol-4-yl) N-(7-acetamido-2,1,3-benzothiadiazol-4-yl).
~.:~p 1 a 2 A solution of 3 g of thionyl chloride in 15 ml of toluene is added to a solution of 3.01 g of 4-tert LO butyl-N-(1,2-diamino-4-phenyl)-1-benzenesulfonamide and 4.1 g of triethylamine in 100 ml of toluene, the mixture is heated for one hour at 110°, worked up in the customary manner and 4-tert-butyl-N-(2,1,3-benzothiadiazol-5-yl)-1-benzenesulfonamide, m.p. 198°, is obtained.
Analogously, by reaction of N-(1,2-diamino-4-phenyl)-1-benzenesulfonamide with thionyl chloride, N-(2,1,3-benzothiadiazol-5-yl)-1-benzenesulfonamide is obtained and by analogous reaction of the following N-(1,2-diamino-4-phenyl)-mZ-1-benzenesulfonamides, in which mZ is 4-fluoro 4-chloro 4-bromo 4-iodo 4-ethyl 4-propyl 4-isopropyl 3,4-dimethyl 2,5-dimethyl 2,5-diethyl CA 02171934 1996-04-10 ~ ~ ~ ~ g ~ 4 2,4-diethyl 2,5-dipropyl 3-acetamido 4-acetamido 2-cyano 3-carboxy 2-trifluoromet"hoxy 3-nitro 4-nitro ~_0 2-nitro-5-methyl 2-methyl-5-nitro 2-ethyl-5-nitro 2,4,6-trimethyl 2,4-dichloro 7_5 2, 5-dichloro 3,4-dichloro 3,5-dichloro 5-bromo-2-methoxy 5-bromo-2-methyl a0 5-bromo-2-ethyl 5-bromo-2-propyl 2,5-difluoro 3,6-difluoro 2,5-dimethoxy 25 3,4-dimethoxy 3-trifluoromethyl 4-trifluoromethyl 3,5-di-(trifluoromethyl) 2,4,5-trichloro 30 2-chloro-4-fluoro 3-chloro-5-fluoro 2-chloro-5-methyl ~~7fi~34 3-chloro-2-methyl 5-chloro-2-methoxy 2-butyl-5-bromo 2-bromo-5-butyl 2-propyl-5-bromo 5-fluoro-2-methyl 2-phenyl with thionyl chloride, the N-(2,1,3-benzothiadiazol-5-yl)-mZ-1-benzenesulfonamides below are obtained in which mZ is 4-fluoro 4-chloro 4-bromo 4 - i odo 4-ethyl 4-propyl 4-isopropyl 3,4-dimethyl 2,5-dimethyl 2,5-diethyl 2,4-diethyl 2,5-dipropyl 3-acetamido 4-acetamido 2-cyano 3-carboxy 2-trifluoromethoxy 3-vitro 4-vitro 2-vitro-5-methyl ' CA 02171934 1996-04-10 ,~ ~ l 1 9 3 4 2-methyl-5-nitro 2-ethyl-5-vitro 2,4,6-trimethyl 2,4-dichloro 2,5-dichloro 3,4-dichloro 3,5-dichloro 5-bromo-2-methoxy 5-bromo-2-methyl 5-bromo-2-ethyl 5-bromo-2-propyl 2,5-difluoro 3,6-difluoro 2,5-dimethoxy 3,4-dimethoxy 3-trifluoromethyl 4-trifluoromethyl 3, 5-di- (trif.luoromethyl) 2,4,5-trichloro 2-chloro-4-fluoro 3-chloro-5-fluoro 2-chloro-5-methyl 3-chloro-2-methyl 5-chloro-2-methoxy 2-butyl-5-bromo 2-bromo-5-butyl 2-propyl-5-bromo 5-fluoro-2-methyl 2-phenyl.

CA 02171934 1996-04-10 ~ ~ 7 1 9 3 4 _ 32 _ Exam.ln a 3 A solution of _ g of 5-dimethylamino-N-(2,1,3-benzoxadiazol-5-yl-1- or -3-N-oxide)-1-naphthalene-sulfonamide (obtainable by heating 5-dimethylamino-N-(1-azido-2-nitro-4-phenyl)-1-naphthalenesulfonamide in glacial acetic acid) ar_d 5 ml of triethyl phosphate in 50 ml of absolute ethanol is heated for 30 minutes at 75°. After removal of the solvent and customary working up, 5-dimethylamina-N-(2,1,3-benzoxadiazol-5-yl)-1-naphthalenesulfonamide is obtained.
Analogously, by reaction of the following 5-dimethylamino-mZ-1-naphthalenesulfanamides in which m2 is N-(4-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4,6-dimethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4,7-dimethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6,7-dimethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-trifluoromethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) .

~~719:34 N-(4,6-dibromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4,7-dibromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6,7-dibromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-bromo-6-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-to oxide) N-(6-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-methyl-6-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) :15N-(4-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-methyl-7-bromo-2,1,3-benzoxadiazol-S-yl-1- or 3-N-oxide) N-(4-bromo-6-ethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-20 oxide) N-(4-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) 25 N-(4-ethyl-6-bromo-2,1,3-benzaxadiazol-5-yl-1- or 3-N-oxide) N-(4-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-3o oxide) N-(4-bromo-6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) ~i71934 N-(4-bromo-7-triyluoromethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-bromo-7-tri~luoromethyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-trifluoromethyl-5-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-4-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-chloro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-chloro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-chloro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-nitro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-nitro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-nitro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-bromo-6-tent-butyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-bromo-7-tart-butyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-bromo-7-tart-butyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-tart-butyl-6-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-tart-butyl-7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-tart-butyl-7-bromo-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-chloro-6-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) CA 02171934 1996-04-10 ~ ~ ~ ~ 9 3 4 N-(6-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-methyl-6-chloro-2,1,3-benzoxadiazol-5-yl-1- or N-oxide) N-(4-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-dimethylamino-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-dimethylamino-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-dimethylamino-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-cyano-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-cyano-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-cyano-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(6-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(4-acetamino-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) ~i71934 N-(6-acetamido-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) N-(7-acetamido-2,1,3-benzoxadiazol-5-yl-1- or 3-N-oxide) with triethyl phosph.ite, the 5-dimethylamino-mZ-1-naphthalenesulfonamides below are obtained in which mZ is :LO N-(4-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-2,1,3-benzoxadiazol-5-yl) N-(7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(4,7-dimethyl-2,1,3-benzoxadiazol-5-yl) :15 N-(6,7-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(7-trifluoromethyl-2,1,3-benzaxadiazol-5-yl) N-(4-bromo-2,1,3-benzoxadiazol-5-yl) 20 N-(6-bromo-2,1,3-benzoxadiazol-5-yl) N-(7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzoxadiazol-5-yl) N-(4,7-dibromo-2,1,3-benzoxadiazol-5-yl) N-(6,7-dibromo-2,1,3-benzoxadiazol-5-yl) ~5 N-(4-bromo-6-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl) :3o N-(6-methyl-7-bromo-2,1,:3-benzoxadiazol-5-yl) N-(4-bromo-6-ethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl) CA 02171934 1996-04-10 ~ ~ ~ 9 3 4 N-(6-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl) N-(4-ethyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-'7-bromo-2,1,3-benzoxadiazol-5-y1) N-(6-trifluoromethyl-7-broma-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-chloro-2,1,3-benzoxadiazol-5-yl) N-(7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-nitro-2,1,3-benzoxadiazol-5-yl) N-(6-nitro-2,1,3-benzoxadiazol-5-yl) N-(7-nitro-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-tent-butyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(4-tert-butyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-tert-butyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-6-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-dimethylamino-2,1,3-benzoxadiazal-5-yl) N-(6-dimethylamino-2,1,3-benzoxadiazal-5-yl) N-(7-dimethylamino-2,1,3-benzoxadiazol-5-yI) N-(4-cyano-2,1,3-benzoxadiazol-5-yl) N-(6-cyano-2,1,3-benzoxadiazol-5-yl) N-(7-cyano-2,1,3-benzoxadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(6-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(4-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(6-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(4-acetamido-2,1,3-benzoxadiazol-5-yl) N-(6-acetamido-2,1,3-benzoxadiazol-5-yl) N-(7-acetamido-2,1,3-benzoxadiazol-5-yl).
Exam lm a 4 A solution of 1 g of 3-nitro-N-(2,1,3 benzothiadiazol-5-yl)-1-benzenesulfonamide in 25 ml of methanol is hydrogenated to completion on 1 g of Raney Nickel at normal pressure and 20°. The solution is filtered, evaporated and 3-amino-N-(2,1,3 benzothiadiazol-5-yl)-1-benzenesulfonamide is obtained.
Analogously, from 4-nitro-N-(2,1,3-benzothiadiazol-5-y1)-1-benzenesulfonamide 2-nitro-5-methyl-N-(2,1,3-benzothiadiazol-5-yl)-1-benzenesulfonamide 2-methyl-5-nitro-N~-(2,1,3-benzothiadiazol-S-yl)-1-benzenesulfonamide 4-nitro-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide 3-nitro-N-(2,1,3-benzoxadiazol-S-yl)-1-benzenesulfonamide 2-nitro-5-methyl-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide 2-methyl-5-nitro-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide the compounds below 4-amino-N-(2,1,3-benzothiadiazol-5-yl)-1-benzenesulfonamide 2-amino-5-methyl-N-(2,1,3-benzothiadiazol-5-yl)-1-benzenesulfonamide 2-amino-5-nitro-N-(2,1,3-benzothiadiazol-5-yl)-1-benzenesulfonamide 4-amino-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide 3-amino-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide 2-amino-5-methyl-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide 2-methyl-5-amino-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide are obtained.
Exam lie S
Analogously to Example 1, by reaction of 5-amino-2,1,3-benzoxadiazole (obtainable by reduction of 5-nitro-2,1,3-benzoxadiazole-1- or 3-N-oxide with triethyl phosphate) with 2-ethylbenzenesulfonyl chloride, 2-ethyl-N-(2,1,3-benzoxadiazol-5-yl)-1-benzenesulfonamide is obtained.
Analogously, from the 5-amino-mZ-2,1,3-benzoxadiazoles ~~71934 _4Q-in which mZ is 4-methyl 6-methyl 7-methyl 4,6-dimethyl 4,7-dimethyl 6,7-dimethyl 4-trifluoromethyl 6-trifluoromethyl 7-trifluoromethyl 4-bromo 6-bromo 7-bromo 4,6-dibromo 4,7-dibromo 6,7-dibromo 4-bromo-6-methyl 4-bromo-7-methyl 6-bromo-7-methyl 4-methyl-6-bromo 4-methyl-7-bromo 6-methyl-7-bromo 4-bromo-6-ethyl 4-bromo-7-ethyl 6-bromo-7-ethyl ' 4-ethyl-6-bromo 4-ethyl-7-bromo 6-ethyl-7-bromo 4-bromo-6-trifluoromethyl 4-bromo-7-trifluoromethyl 6-bromo-7-trifluoromethyl 4-trifluoromethyl-6-bromo 4-trifluoromethyl-7-bromo 6-trifluoromethyl-~-bromo 4-chloro 6-chloro 7-chloro 4-nitro 6-nitro 7-nltr0 4-bromo-6-tent-butyl 4-bromo-7-tert-butyl 6-bromo-7-tert-butyl 4-tert-butyl-6-bromo 4-tert-butyl-7-bromo 5-tert-butyl-7-bromo 4-chloro-6-methyl 4-chloro-7-methyl 6-chloro-7-methyl 4-methyl-6-chloro 4-methyl-7-chloro 6-methyl-7-chloro 4-dimethylamino 6-dimethylamino 7-dimethylamino 4-cyano 6-cyano 7-cyano 4-methoxycarbonyl 6-methoxycarbonyl 7-methoxycarbonyl 4-ethoxycarbonyl 6-ethoxycarbonyl ~....
~t7?934 7-ethoxycarbonyl 4-acetamido 6-acetamido 7-acetamido by reaction with 2-ethylbenzenesulfonyl chloride the 2-ethyl-mZ-1-benzenesulfonamides below are obtained in which mZ is N-(4-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-2,1,3-benzoxadiazol-5-yl) N-(7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(4,7-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(6,7-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-2,1,3-benzoxadiazol-5-yl) N-(7-bromo-2,1,3-benzaxadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzoxadiazol-5-yl) N-(4,7-dibromo-2,1,3-benzoxadiazol-5-yl) N-(6,7-dibromo-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-methyl-2,1,3-benzaxadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-ethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl) p ~~71934 N-(6-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl) N-(4-ethyl-6-bromo--2,1,3-benzoxadiazol-5-yl) N-(4-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) J N-(4-bromo-6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-chloro-2,1,3-benzoxadiazol-5-yl) N-(7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-vitro-2,1,3-benzoxadiazol-5-yl) N-(6-vitro-2,1,3-benzoxadiazol-5-yl) N-(7-vitro-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-tart-butyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-tart-butyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-tart-butyl-2,1,3-benzoxadiazol-5-yl) 2G N-(4-tart-butyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-tart-butyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-tart-butyl-7-brorno-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-6-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-dimethylamino-2,1,3-benzoxadiazol-5-yl) 3G N-(6-dimethylamino-2,1,3-benzoxadiazol-5-yl) N-(7-dimethylamino-2,1,3-benzoxadiazol-5-yl) N-(4-cyano-2,1,3-benzoxadiazol-5-yl) ...-.-_~,~~_,.,..,.._.....~._.......~..~,..",.,.," ~ ,~..~...,.~...~...-......_........__....._..__._.~..~.

~ 171934 N-(6-cyano-2,1,3-benzoxadiazol-5-yl) N-(7-cyano-2,1,3-benzoxadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(6-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(4-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(6-ethoxycarbanyl-2,1,3-benzoxadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(4-acetamido-2,1,3-benzoxadiazal-5-yl) N-(6-acetamido-2,1,3-benzoxadiazol-5-yl) N-(7-acetamido-2,1,3-benzoxadiazal-5-yl).
By corresponding reactions with 2-ethyl-5-bromobenzenesulfonyl chloride the 2-ethyl-5-bromo-mZ-1-benzenesulfonamides below are obtained in which mZ is N-(4-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-2,1,3-benzoxadiazol-5-yl) N-(7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzoxadiazal-5-yl) N-(4,7-dimethyl-2,1,3-benzaxadiazol-5-yl) N-(6,7-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) <?5 N-(6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-~(7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-2,1,3-benzoxadiazal-5-yl) N-(6-bromo-2,1,3-benzoxadiazol-5-yl) N-(7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzoxadiazal-5-yl) N-(4,7-dibromo-2,1,3-benzoxadiazol-5-yl) N-(6,7-dibromo-2,1,3-benzoxadiazal-5-yl) ai71934 N-(4-bromo-6-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-ethyl-2,1.,3-benzoxadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl) N-(4-ethyl-6-bromo-2,1,3-benzoxadiazol-5-y1) N-(4-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-ethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-trifluoromethyl-2,2,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-chloro-2,1,3-benzoxadiazol-5-yl) N-(7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-vitro-2,1,3-benzoxadiazol-5-yl) N-(6-vitro-2,1,3-benzoxadiazol-5-yl) N-(7-vitro-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(4-tert-butyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-tent-butyl-7-brorno-2,1,3-benzoxadiazol-5-yl) N-(6-tent-butyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-6-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) .....__.__-..._.,.._..__.~_..._.._..__.. ~""~.~,~ r.~~..._..
....._..._.._._..___,.__-__~__... __ _..

N-(6-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-dimethylamino-2,1,3-benzoxadiazol-5-yl) N-(6-dimethylamino--2,1,3-benzoxadiazol-5-yl) N-(7-dimethylamino-2,1,3-benzoxadiazol-5-yl) N-(4-cyano-2,1,3-benzoxadiazol-5-yl) N-(6-cyano-2,1,3-benzoxadiazol-5-yl) to N-(7-cyano-2,1,3-benzoxadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(6-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(4-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(6-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(4-acetamido-2,1,3-benzoxadiazol-5-yl) N-(6-acetamido-2,1,3-benzoxadiazol-5-yl) N-(7-acetamido-2,1,3-benzoxadiazol-5-yl), and by analogous reaction with 2-propyl-5-bromobenzenesulfonyl chloride the 2-propyl-5-bromo-mZ-1-benzenesulfonamides below are obtained in which mZ is N-(4-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-2,1,3-benzoxadiazol-5-yl) N-(7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(4,7-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(6,7-dimethyl-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(7-triflucromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-2,1,3-benzoxadiazol-5-yl) N-(7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzaxadiazol-5-yl) N-(4,7-dibromo-2,1,3-benzoxadiazol-5-yl) N-(6,7-dibromo-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-methyl-2,1,3-benzoxadiazal-5-yl) l0 N-(4-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-bromo-2,1,3-benzaxadiazol-S-yl) N-(4-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-6-ethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-ethyl-2,1,3-benzoxadiazal-5-yl) N-(4-ethyl-6-bromo-2,1,3-benzoxadiazal-5-yl) N-(4-ethyl-7-bromo-2,1,3-benzoxadiazal-5-yl) N-(6-ethyl-7-bromo-2,1,3-benzoxadiazal-5-yl) N-(4-bromo-6-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-trifluoromethyl-2,1,3-benzaxadiazol-5-yl) N-(6-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(6-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-chloro-2,1,3-benzoxadiazol-5-yl) N-(7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-nitro-2,1,3-benzaxadiazol-S-yl) N-(6-nitro-2,1,3-benzoxadiazol-5-yl) N-(7-nitro-2,1,3-benzoxadiazol-5-yl) .._ _. ..~ .. _..... _....-_~__.-..,-.._ ._.~,-...-,-.,..~~...._.. -,._,...,--,~".~"".,~""~...".,."-,_..........._....

~. 171934 N-(4-bromo-6-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(4-bromo-7-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(6-bromo-7-tert-butyl-2,1,3-benzoxadiazol-5-yl) N-(4-tert-butyl-6-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-tert-butyl-7-bromo-2,1,3-benzaxadiazol-5-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-5-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(6-chloro-7-methyl-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-6-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(6-methyl-7-chloro-2,1,3-benzoxadiazol-5-yl) N-(4-dimethylamino-2,1,3-benzoxadiazol-5-yl) N-(6-dimethylamino-2,1,3-benzoxadiazol-5-yl) :L5 N-(7-dimethylamino-2,1,3-benzaxadiazol-5-yl) N-(4-cyano-2,1,3-benzoxadiazol-5-yl) N-(6-cyano-2,1,3-benzoxadiazol-5-yl) N-(7-cyano-2,1,3-benzoxadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) :20 N-(6-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(4-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(6-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzoxadiazol-5-yl) 25 N-(4-acetamido-2,1,3-benzoxadiazol-5-yl) N-(6-acetamido-2,1,3-benzoxadiazol-5-yl) N-(7-acetamido-2,1,3-benzoxadiazol-S-yl).
Analogously, from the 5-amino-mZ-2,1,3-30 benzothiadiazoles ir. which mZ is ~~11934 ~-methyl 6-methyl 7-methyl ~,6-dimethyl Q,7-dimethyl 6,7-dimethyl 4-trifluoromethyl 6-trifluoromethyl 7-trifluoromethyl :l O ~ -bromo 6-bromo 7-bromo 4,6-dibromo ~,7-dibromo :L5 6,7-dibromo 4-bromo-6-methyl 4-bromo-7-methyl 6-bromo-7-methyl 4-methyl-6-bromo 20 4-methyl-7-bromo 6-methyl-7-bromo a-bromo-6-ethyl 4-bromo-7-ethyl 6-bromo-7-ethyl 4-ethyl-6-bromo 4-ethyl-7-bromo 6-ethyl-7-bromo 4-bromo-6-trifluoramethyl 4-bromo-7-trifluoromethyl :30 6-bromo-7-trifluoromethyl 4-trifluoromethyl-6-bromo 4-trifluoromethyl-7-bromo _....._..~..~.......~.~._..~.~..."..._~..,...,..~_...~.._.__-_........,.._..~,.,.m"~..,.~","~,.",~ ~~,~..~"~»..~.-..-.... ._......_.__ ____._ _._._...._ ...__..._ ._. ._...._..._ ~~ 7 ~ 9 3 ~.

6-trifluoromethyl-7-bromo 4-chloro 6-chloro 7-chloro 4-nitro 6-nitro 7-nitro 4-bromo-6-tert-butyl 4-bromo-7-tent-butyl .l0 6-bromo-7-tent-butyl 4-tert-butyl-6-bromo 4-tert-butyl-7-bromo 6-tert-butyl-7-bromo 4-chloro-6-methyl :L5 4-chloro-7-methyl 6-chloro-7-methyl 4-methyl-6-chloro 4-methyl-7-chloro 6-methyl-7-chloro 20 4-dimethylamino 6-dimethylamino 7-dimethylamino 4-cyano 6-cyano 25 7-cyano 4 --methoxycarbonyl 6-methoxycarbonyl 7-methoxycarbonyl 4-ethoxycarbonyl :30 6-ethoxycarbonyl 7-ethoxycarbonyl 4-acetamido ~~71~~4 _ 51 _ 6-acetamido 7-acetamido by reaction with 2-ethylbenzenesulfonyl chloride the 2-ethyl-mZ-1-benzenesulfonamides below are obtained in which mZ is N-(4-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-2,1,3-benzothiadiazol-5-yl) N-(7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(4,7-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(6,7-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-2,1,3-benzothiadiazol-5-yl) N-(7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzothiadiazol-5-yl) N-(4,7-dibromo-2,1,3-benzothiadiazol-5-yl) N-(6,7-dibromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-methy:L-2,1,3-benzathiadiazol-5-yl) N-(4-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-ethyl-6-bromo-2,1,3-benzothiadiazol-5-yl) ~17193~

N-(4-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-trifluoramethyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzothiadiazol-5-l0 yl) N-(4-trifluoromethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-2,1,3-benzothiadiazol-5-yl) N-(6-chloro-2,1,3-benzothiadiazol-5-yl) N-(7-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-vitro-2,1,3-benzothiadiazol-5-yl) N-(6-vitro-2,1,3-benzothiadiazol-5-yl) N-(7-vitro-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-tent-butyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-tent-butyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-tent-butyl--2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-7-broma-2,1,3-benzothiadiazol-5-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-5-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-chloro-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-5-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-7-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-dimethylamino-x,1,3-benzothiadiazol-5-yl) N-(6-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(7-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(4-cyano-2,1,3-benzothiadiazol-5-yl>
N-(6-cyano-2,1,3-benzothiadiazol-5-yl) N-(7-cyano-2,1,3-benzothiadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) l0 N-(4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yI) N-(4-acetamido-2,1,3-benzothiadiazol-5-yl) N-(6-acetamido-2,1,3-benzothiadiazol-5-yl) N-(7-acetamido-2,1,3-benzothiadiazol-5-yl), and by analogous reaction with 2-ethyl-5-bromobenzenesulfonyl chloride the 2-ethyl-5-bromo-mZ-1-benzenesulfonamides below are obtained in which mZ is N-(4-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-2,1,3-benzothiadiazol-5-yl) N-(7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(4,7-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(6,7-dimethyl-2,1,3-benzothiadiazol-5-y1) N-(4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-2,1,3-benzothiadiazol-5-yl) M......-.-......._.-..-....,.....-_._..,-..-,M"~"",~.,"-.,.",~"A,."~.""~,~~,~"~""",~"",w~"~..-" "~~~"."~,w",a,~~,""","~",~""",-,,.-.-,....._._..._.._......__.____... ~.-__._.._. .. ..... . _ N-(7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzothiadiazol-5-yl) N-(4,7-dibromo-2,1,3-benzothiadiazol.-5-yl) N-(6,7-dibromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzothiadiazol-5-y1) N-(6-bromo-7-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-ethyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-2,1,3-benzothiadiazol-5-yl) N-(6-chloro-2,1,3-benzothiadiazol-5-yl) N-(7-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-nitro-2,1,3-benzothiadiazol-5-yl) i 71934 _ 55 -N-(6-nitro-2,1,3-benzothiadiazol-5-yl) N-(7-nitro-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6~-tert-butyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-tert-butyl-1,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-tert-butyl-2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-'7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-6-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-chloro-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-6-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3=benzothiadiazol-5-yl) N-(6-methyl-7-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(6-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(7-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(4-cyano-2,1,3-benzothiadiazol-5-yl) N-(6-cyano-2,1,3-benzothiadiazol-5-yl) N-(7-cyano-2,1,3-benzothiadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(4-acetamido-2,1,3-benzothiadiazol-5-yl) N-(6-acetamido-2,1,3-benzothiadiazol-5-yl) N-(7-acetamido-2,1,3-benzothiadiazol-5-yl), ' CA 02171934 1996-04-10 ~t71434 ~:.~~..
_ 56 _ and by analogous reaction with 2-propyl-5-bromobenzenesulfonyl chloride the 2-propyl-5-bromo-mZ-1-benzenesulfonamides below are obtained in which mZ is N-(4-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-2,1,3-benzothiadiazol-5-y1) N-(7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4,6-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(4,7-dimethyl-2,1,3-benzothiadiazol-5-y1) N-(6,7-dimethyl-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) a5 N-(4-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-2,1,3-benzothiadiazol-5-yl) N-(7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4,6-dibromo-2,1,3-benzathiadiazol-5-yl) N-(4,7-dibromo-2,1,3-benzothiadiazol-5-yl) N-(6,7-dibromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-6-bromo-2,1,3-benzothiadiazol-5-yl) '<?5 N-(4-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-ethyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-ethyl-2,1,3-benzothiadiazol-5-yl) N-(4-ethyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-ethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) ~17~934 N-(4-bromo-6-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-trifluoromethyl-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-trifluoromethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-trifluoromethyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-2,1,3-benzothiadiazol-5-yl) N-(6-chloro-2,1,3-benzothiadiazol-5-yl) N-(7-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-nitro-2,1,3-benzothiadiazol-5-yl) N-(6-nitro-2,1,3-benzothiadiazol-5-yl) N-(7-nitro-2,1,3-benzothiadiazol-5-yl) N-(4-bromo-6-tert-butyl-2,1,3-benzothiadiazol-5-yl) N-(4-broma-7-tent-butyl-2,1,3-benzothiadiazol-5-yl) N-(6-bromo-7-tert-butyl-2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-6-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-tert-butyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-6-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-chloro-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(6-chloro-7-methyl-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-5-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-methyl-7-chloro-2,1,3-benzothiadiazol-5-yl) N-(6-methyl-7-chloro-2,1,3-benzothiadiazol-5-yl) N-(4-dimethylamino-2,1,3-benzothiadiazol-5-yl) N-(6-dimethylamino-2,1,3-benzothiadiazol-5-yl) ;. 2 i 71934 _ 5g _ N-(7-dimethylamina-2,1,3-benzothiadiazol-5-yl) N-(4-cyano-2,1,3-benzothiadiazol-5-yl) N-(6-cyano-2,1,3-benzothiadiazol-5-yl) N-(7-cyano-2,1,3-benzothiadiazol-5-yl) N-(4-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-methoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(6-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(7-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl) N-(4-acetamido-2,1,3-benzothiadiazol-5-yl) N-(6-acetamido-2,1,3-benzothiadiazol-5-yl) N-(7-acetamido-2,1,3-benzathiadiazol-5-yl).
F~S.am~ a 6 Analogously to Example 1, by reaction of 6-amino-1,2,5-oxadiazolol3,4-b]pyridine with "A"
5-dimethylamino-N-(1,2,5-oxadiazolo[3,4-b]pyridin-6-yl)-1-naphthalenesulfonamide is obtained.
Analogously, from the following mZ-6-amino-1,2,5-oxadiazolo(3,4-b]pyridines in which mZ is 5-methyl 7-methyl 5,7-dimethyl 5-trifluoromethyl 7-trifluoromethyl 5-bromo 7-bromo 5,7-dibromo 5-bromo-7-methyl ~j71934 _. 59 _ 5-methyl-7-bromo 5-bromo-7-ethyl 5-ethyl-7-bromo 5-bromo-7-trifluoromethyl 5-trifluoromethyl-7-bromo 5-chloro 7-chloro 5-nitro 7-nitro 5-bromo-7-tert-butyl 5-tert-butyl-7-bromo 5-chloro-7-methyl 5-methyl-7-chloro 5-dimethylamino 7-dimethylamino 5-cyano 7-cyano 5-methoxycarbonyl 7-methoxycarbonyl 5-ethoxycarbonyl 7-ethoxycarbonyl 5-acetamino 7-acetamide by reaction with "A", the 5-dimethylamino-N-(mZ-1,2,5-oxadiazolo[3,4-b~pyridin-6-yl)-1-naphthalene-sulfonamides below are obtained in which mZ is 5-methyl 7-methyl 5,7-dimethyl 5-trifluoromethyl 7-trifluoromethyl 5-bromo 7-bromo 5,7-dibromo 5-bromo-7-methyl 5-methyl-7-'bromo 5-bromo-7-ethyl 5-ethyl-7-bromo :LO 5-bromo-7-trifluoromethyl 5-trifluoromethyl-7-bromo 5-chloro 7-chloro 5-nitro :L5 7-nitro 5-bromo-7-tent-butyl 5-tert-butyl-7-bromo 5-chloro-7-methyl 5-methyl-7-chloro ?0 5-dimethylamino 7-dimethylamino 5-cyano 7-cyano 5-methoxycarbonyl 25 7-methoxycarbonyl 5-ethoxycarbonyl 7-ethoxycarbonyl 5-acetamido 7-acetamido.
Analogously, by reaction of 6-amino-1,2,5-thiadiazolo[3,4-b]pyridine with "A", 5-dimethylamino-N-(1,2,5-thiadiazolo[3,4-b]pyridin-6-yl)-1-naphthalenesulfonamide is obtained.
Analogously, from the following mZ-6-amino-1,2,5-thiadiazolo[3,4-b]pyridines in which mZ is 5-methyl 7-methyl 5,7-dimethyl 5-trifluoromethyl 7-trifluoromethyl 5-bromo 7-bromo 5,7-dibromo 5-bromo-7-methyl 5-methyl-7-bromo 5-bromo-7-ethyl 5-ethyl-7-bromo 5-bromo-7-trifluoromethyl 5-trifluoromethyl-7-bromo 5-chloro 7-chloro 5-nitro 7-nitro 5-bromo-7-tert-butyl 5-tent-butyl-7-bromo 5-chloro-7-methyl 5-methyl-7-chloro 5-dimethylamino 7-dimethylamino 5-cyano 7-cyano - ~2 -5-methoxycarbonyl 7-methoxycarbonyl 5-ethoxycarbonyl 7-ethoxycarbonyl 5-acetamido 7-acetamido by reaction with "A", the 5-dimethylamino-N-(mZ-1,2,5-thiadiazolo[3,4-b]pyridin-6-yl)-1-naphthalene-sulfonamides below are obtained in which mZ is 5-methyl -~ .
7-methyl 5,7-dimethyl 5-trifluoromethyl 7-trifluoromethyl 5-bromo 7-bromo 5,7-dibromo 5-bromo-7-methyl 5-methyl-7-bromo 5-bromo-7-ethyl 5-ethyl-7-bromo 5-bromo-7-trifluoromethyl 5 ~- t ri f luoromethyl - 7 -bromo 5-chloro 7-chloro 5-nitro 7-nitro 5-bromo-7-tent-butyl 5-tert-butyl-7-bromo 5-chloro-7-methyl 5-methyl-7-c~:lorc 5-dimethylam=_no 7-dimethylamino 5-cyano 7-cyano 5-methoxycarbonyl 7-methoxycarbonyl 5-ethoxycarbonyl 7-ethoxycarbonyl 5-acetamido 7-acetamido.
Analogously, by reaction of 7-amino-1,2,5-oxadiazolo[3,4-b]pyridine with "A" 5-dimethyl-amino-N-(1,2,5-oxadiazolo[3,4-b]pyridin-7-yl)-1-naphthalenesulfonamide is obtained.
Analogously, from the following mZ-7-amino-1,2,5-oxadiazolo[3,4-b]pyridines in which mZ is 5-methyl 6-methyl 5,6-dimethyl 5-trifluoromethyl 6-trifluoromethyl 5-bromo 6-bromo 5,6-dibromo 5-bromo-6-methyl 5-methyl-6-bromo 5-bromo-6-ethyl ,171934 5-ethyl-6-bromo 5-bromo-6-trifluoromethyl 5-trifluoromethyl-6-bromo 5-chloro 6-chloro 5-nitro 6-nitro 5-bromo-6-tent-butyl 5-tert-butyl-6-bromo 5-chloro-6-methyl 5-methyl-6-chloro 5-dimethylamino 6-dimethylamino 5-cyano 6-cyano 5-methoxycarbonyl 6-methoxycarbonyl 5-ethoxycarbonyl 6-ethoxycarbonyl 5-acetamido 6-acetamido by reaction with "A", the 5-dimethylamino-N-(mZ-1,2,5-oxadiazolo[3,4-b]pyridin-6-yl)-1-naphthalene-sulfonamides below are obtained in which mZ is ' 5-methyl 6-methyl 5,6-dimethyl 5-trifluoromethyl 6-trifluoromethyl _._u.. __ .. . _ _........-. "~.
---~.,~ _..-___.~. _._. _ . . .._.....__._.

5-bromo 6-bromo 5,6-dibromo 5-bromo-6-methyl 5-methyl-6-bromo 5-bromo-6-ethyl 5-ethyl-6-bromo 5-bromo-6-trifluoromethyl 5-trifluoromethyl-6-bromo 5-chloro 6-chloro 5-nitro 6-nitro 5-bromo-6-tert-butyl 5-tert-butyl-6-bromo 5-chloro-6-methyl 5-methyl-6-chloro 5-dimethylamino 6-dimethylamino 5-cyano 6-cyano 5-methoxycarbonyl 6-methoxycarbonyl 5-ethoxycarbonyl 6-ethoxycarbonyl 5-acetamido 6-acetamido.
Analogously, by reaction of 7-amino-1,2,5-thiadiazolo[3,4-b]pyridine with "A", 5-dimethyl-N-(1,2,5-thiadiazolo[3,4-b]pyridin-7-yl)-1-naphthalene-sulfonamide is obtained.

...~,~
l 7 ~ 934 Analogously, from the following mZ-7-amino-1,2,5-thiadiazolo[3,4-b]pyridines in which mZ is 5-methyl 6-methyl 5,6-dimethyl 5-trifluoromethyl 6-trifluoromethyl 5-bromo 6-bromo 5,6-dibromo 5-bromo-6-methyl 5-methyl-6-bromo 5-bromo-6-ethyl 5-ethyl-6-bromo 5-bromo-6-trifluoromethyl 5-trifluoromethyl-6-bromo 5-chloro 6-chloro 5-nitro 6-nitro 5-bromo-6-tert-butyl 5-tert-butyl-6-bromo 5-chloro-6-methyl 5-methyl-6-chloro 5-dimethylamino 6-dimethylamino 5-cyano :30 6-cyano 5-methoxycarbonyl 6-methoxycarbonyl ..._..._. _ _T . ..._..__.~._-.,..~..-....,-_,...~,~ .,._..__~.__._..__._.--..___..._.__ ....

Zi?1934 5-ethoxycarbonyl 6-ethoxycarbonyl 5-acetamido 6-acetamido by reaction with "A" the 5-dimethylamino-N-(mZ-1,2,5-thiadiazolo[3,4-b]pyridin-6-yl~-1-naphthalene-sulfonamides below are obtained in which mZ is 5-methyl 6-methyl 5,6-dimethyl 5-trifluoromethyl 6-trifluoromethyl 5-bromo 6-bromo 5,6-dibromo 5-bromo-6-methyl 5-methyl-6-bromo 5-bromo-6-ethyl 5-ethyl-6-bromo 5-bromo-6-trifluoromethyl 5-trifluoromethyl-6-bromo 5-chloro 6-chloro 5-nitro 6-nitro 5-bromo-6-tert-butyl 5-tert-butyl-6-bromo 5-chloro-6-methyl 5-methyl-6-chloro _. ....._......_._._.. .~..__.. _._....

5-dimethylamino 6-dimethylamino 5-cyano 6-cyano 5-methoxycarbonyl 6-methoxycarbonyl 5-ethoxyc~,rbonyl 6-ethoxycarbonyl 5-acetamido 6-acetamido.
Exa ~,. a 7 Analogously to Example 1, by -.reaction of 4-amino-2,1,3-benzoxadiazole with "A", 5-dimethylamino-N-(2,1,3-benzoxadiazol-4-yl?-1-naphthalenesulfonamide is obtained, and from the following 4-amino-mZ-2,1,3-benzoxadiazoles in which mZ is ?0 5-methyl 6-methyl 7-methyl 5,6-dimethyl 5,7-dimethyl a?5 6, 7-dimethyl 5-trifluoromethyl 6-trifluoromethyl 7-trifluoromethyl 5-bromo 30 6-bromo 7-bromo 5,6-dibromo ~1~1934 5,7-dibromo 6,7-dibromo 5-bromo-6-methyl 5-bromo-7-methyl 6-bromo-7-methyl 5-methyl-6-bromo 5-methyl-7-bromo 6-methyl-7-bromo 5-bromo-6-ethyl :LO 5-bromo-7-ethyl 6-bromo-7-ethyl 5-ethyl-6-bromo 5-ethyl-7-bromo 6-ethyl-7-bromo :L5 5-bromo-6-trifluoromethyl 5-bromo-7-trifluoromethyl 6-bromo-7-trifluoromethyl 5-trifluoromethyl-6-bromo 5-trifluoromethyl-7-bromo 20 6-trifluoromethyl-7-bromo 5-chloro 6-chloro 7-chloro 5-nitro 25 6-nitro 7-nitro 5-bromo-6-tert-butyl 5-bromo-7-tent-butyl 6-bromo-7-tert-butyl 30 5-tert-butyl-6-bromo 5-tert-butyl-7-bromo 6-tert-butyl-7-bromo _ 70 -5-chloro-6-methyl 5-chloro-7-methyl 6-chloro-7-methyl 5-methyl-6-chlorc 5-methyl-7-chloro 6-methyl-7-chloro 5-dimethylarrrinb 6-dimethylamino 7-dimethylamino 5-cyano 6-cyano 7-cyano 5-methoxycarbonyl 6-methoxycarbonyl 7-methoxycarbonyl 5-ethoxycarbonyl 6-ethoxycarbonyl 7-ethoxycarbonyl 5-acetamido 6-acetamido 7-acetamido with "A", the 5-dimethylamina-mZ-1-naphthalene-sulfonamides below are obtained in which mZ is N-(5-methyl-2,1,3-benzoxadiazol-4-yl) N-(6-methyl-2,1,3-benzoxadiazol-4-yl) N-(7-methyl-2,1,3-benzaxadiazol-4-yl) N-(5,6-dimethyl-2,1,3-benzaxadiazol-4-yl) N-(5,7-dimethyl-2,1,3-benzaxadiazol-4-y1) N-(6,7-dimethyl-2,1,3-benzoxadiazol-4-yl) ~17i934 N-(5-trifluoromeLhyl-2,1,3-benzoxadiazol-4-yl) N-(6-trifluorome'hyl-2,1,3-benzoxadiazol-4-yl) N-(7-trifluo~ome~hyi-2,1,3-benzoxadiazol-4-yl) N-(5-bromo-2,1,3-ben.zoxadiazol-4-yl) N-(6-bromo-2,1,3-be-izoxadiazol-4-yl) N-(7-bromo-2,1,3-benzoxadiazol-4-yl) N-(5,6-dibrcmo-2,1,3-benzoxadiazal-4-yl) N-(5,7-dibromo-2,1,3-benzoxadiazol-4-yl) N-(6,7-dibromo-2,1,3-benzoxadiazol-4-yl) N-(5-bromo-5-methyl-2,1,3-benzoxadiazol-4-yl) N-(5-bromo-7-methyl-2,1,3-benzoxadiazol-4-yl) N-(6-bromo-7-methyl-2,1,3-benzoxadiazol-4-yl) N-(5-methyl-5-bromo-2,1,3-benzoxadiazol-4-yl) N-(5-methyl-7-bromo-2,1,3-benzoxadiazol-4-yl) :15 N-(6-methyl-7-bromo-2,1,3-benzoxadiazol-4-yl) N-(5-bromo-6-ethyl-2,1,3-benzoxadiazol-4-yl) N-(5-bromo-7-ethyl-2,1,3-benzoxadiazal-4-yl) N-(6-bromo-7-ethyl-2,1,3-benzoxadiazol-4-yl) N-(5-ethyl-6-bromo-2,1,3-benzoxadiazol-4-yl) N-(5-ethyl-7-bromo-2,1,3-benzoxadiazol-4-yl) N-(6-ethyl-7-bromo-2,1,3-benzoxadiazol-4-yl) N-(5-bromo-6-trifluoromethyl-2,1,3-benzoxadiazol-4-yl) N-(5-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-4-yl) N-(6-bromo-7-trifluoromethyl-2,1,3-benzoxadiazol-4-yl) N-(5-trifluoromethyl-6-bromo-2,1,3-benzoxadiazol-4-yl) D1-(5-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-4-yl) N-(6-trifluoromethyl-7-bromo-2,1,3-benzoxadiazol-4-yl) N-(5-chloro-2,1,3-benzoxadiazol-4-yl) N-(6-chloro-2,1,3-benzoxadiazol-4-y1) N-(7-chloro-2,1,3-benzoxadiazol-4-yl) N-(5-nitro-2,1,3-benzoxadiazol-4-yl) N-(6-nitro-2,1,3-benzoxadiazol-4-yl) *, ~1?I934 N-(7-nitro-2,1,3-banzoxadiazol-4-yl) N-(5-bromo-6-tert-butyl-'3,1,3-benzoxadiazol-4-yl) N-(S-bromo-7-tert-butyl-3,1,3-banzoxadiazol-4-yl) N-(6-bromo-7-tert-butyl-2,1,3-benzoxadiazol-4-yl) N-(5-tert-butyl-5-bromo-2,1,3-benzoxadiazol-4-yl) N-(5-tert-butyl-7-bromo-2,1,3-benzoxadiazol-4-yl) N-(6-tert-butyl-7-bromo-2,1,3-benzoxadiazol-4-yl) N-(5-chloro-6-methyl-2,1,3-benzoxadiazol-4-yl) N-(5-chloro-7-methyl-2,1,3-benzoxadiazol-4-yl) 7_0 N-(6-chloro-7-methyl-2,1,3-benzoxadiazol-4-yl) N-(5-methyl-6-chloro-2,1,3-benzoxadiazol-4-yl) N-(5-methyl-7-chloro-2,1,3-benzoxadiazol-4-yl) N-(6-methyl-7-chloro-2,1,3-benzaxadiazol-4-yl) N-(5-dimethylamino-2,1,3-benzoxadiazol-4-yl) N-(6-dimethylamino-2,1,3-benzoxadiazol-4-yl) N-(7-dimethylamino-2,1,3-benzoxadiazol-4-yl) N-(5-cyano-2,1,3-benzoxadiazol-4-yl) N-(6-cyano-2,1,3-benzoxadiazol-4-yl) N-(7-cyano-2,1,3-benzoxadiazol-4-yl) <'?0 N-(5-methoxycarbonyl-2,1,3-benzoxadiazol-4-yl) N-(6-methoxycarbonyl-2,1,3-benzoxadiazol-4-yl) N-(7-methoxycarbonyl-2,1,3-benzoxadiazol-4-yl) N-(5-ethoxycarbonyl-2,1,:3-benzoxadiazol-4-yl) N-(6-ethoxycarbonyl-2,1,3-benzoxadiazol-4-yl) a?5 N-(7-ethoxycarbonyl-2,1,3-benzoxadiazol-4-yl) N-(5-acetamido-2,1,:3-benzoxadiazol-4-yl) N-(6-acetamido-2,1,3-benzoxadiazol-4-yl) N-(7-acetamido-2,1,3-benzoxadiazol-4-yl).
30 Exam In a 8-A mixture of 4.6 g of S-dimethylamino-N-(S-bromo-6-ethyl-2,1,3-benzoxadiazol-4-yl)-CA 02171934 1996-04-10 ~ ~ ~ j 9 3 4 1-naphthalenesul~onamide and 1.3 g of copper cyanide is heated for 8 hours at 120° in 30 ml of pyridine. The mixture is poured onto aqueous ammonia solution, worked up in the customary manner and 5-dimethylamino-N-(5-cyano-6-ethyl-2,1,3-benzoxadiazol-4-yl)-1-naph-thalenesulfonamide is obtained.
Exam~2, a 9 A solution of 1 g of 5-dimethylamino-N-(5-cyano-6-ethyl-2,1,3-benzoxadiazol-4-yl)-1-naph-thalenesulfonamide and 0.7 g of potassium hydroxide in ml of ethanol and 5 ml of water is boiled with stirring for 8 hours. The solvents are removed, the residue is dissolved in water and treated with 15 hydrochloric acid and 5-dimethylamino-N-(5-carboxy-6-ethyl-2,1,3-benzoxadiazol-4-yl)-1-naphthalene-sulfonamide is obtained.
Exam~2. a 10 20 A solution of 1 g of 5-dimethylamino-N-(5-carboxy-6-ethyl-2,1,3-benzoxadiazol-4-yl)-1-naph-thalenesulfonamide, 0.5 ml of cone sulfuric acid and ml of ethanol is heated for 6 hours at 80°. The solvent is removed, the residue is worked up in the 25 customary manner and 5-dimethylamino-N-(5-ethoxy-carbonyl-6-ethyl-2,1,3-benzoxadiazol-~-yl)-1-naph-thalenesulfonamide is obtained.
E~i~.h 11 30 A solution of 6 g of 4-amino-N-(2,1,3-benzo-thiadiazol-5-yl)-1-benzenesulfonamide and 0.5 g of titanium tetrachloride in 100 ml of methanol is treated CA 02171934 1996-04-10 ~ ~ ~ ~ ~ 3 4 _ 74 _ with 1 ml of freshly distilled acetaldehyde. 4 g of sodium cyanoborohydride are then added thereto and the mixture is stirred for 30 hours. Cold half-concentrated hydrochloric acid is added thereto, the mixture is worked up in the customary manner and 4-ethylamino-N-(2,1,3-benzothiadiazol-5-yl)-1-benzenesulfonamide is obtained.
Example 12 A solution of 1 g of 4-isocyanato-N-(4-bromo-7-methyl-2,1,3-benzothiadiazol-5-yl)-1-benzenesulfon-amide [obtainable by reaction of 4-bromo-5-amino-7-methyl-2,1,3-benzothiadiazole with 4-isocyanato-benzenesulfonyl chloride] in 80 ml of toluene is treated with 0.5 g of pyrrolidine and stirred for 1 hour at 90°. After customary working up, 4-pyrrolidinoamido-N-(4-bromo-7-methyl-2,1,3-benzothia-diazol-5-yl)-1-benzenesulfonamide is obtained.
The following examples relate to pharmaceutical preparations:
Example A: Injection vials A solution of 100 g of an active compound of the formula I and 5 g of disodium hydrogenphosphate is adjusted to pH 6.5 in 3 1 of double-distilled water using 2N hydrochloric acid, sterile-filtered, filled into injection vials, lyophilized under sterile conditions and aseptically sealed. Each injection vial contains 5 mg of active compound.

CA.02171934 1996-04-10 ~ ~ 7 ~ 9 ~ 4 ~H~, _7r.~_ Example B: Suppositories A mixture of 20 g of an active compound of the formula I is fused with 100 g of Soya lecithin and 1400 g of cocoa butter, poured into moulds and allowed to cool. Each suppository contains 20 mg of active compound.
Example C: Solution A solution is prepared from 1 g of an active compound of the formula I, 9.38 g of NaH2P04.2H20, 28.48 g of Na2HP04. 12H20 and 0.1 g of benzalkonium chloride in 940 ml of double-distilled water. The solution is adjusted to pH 6.8, made up to 1 1 and sterilized by irradiation. This solution can be used in the form of eye drops.
Example D: Ointments 500 mg of an active compound of the formula I
is mixed with 99.5 g of petroleum jelly under aseptic conditions.
Example E: Tablets A mixture of 1 kg of active compound of the formula I, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is compressed in a customary manner to give tablets such that each tablet contains 10 mg of active compound.
Example F: Coated tablets Analogously to Example E, tablets are pressed which are then coated in a customary manner with a ' CA 02171934 1996-04-10 ~ 171934 covering of sucrose, potato starch, talc, tragacanth anti colourant .
Example G: Capsules 2 kg of active compound of the formula I are filled into hard gelatin capsules in a customary manner such that each capsule contains 20 mg of the active compound.
Example H: Ampoules A solution of 1 kg of active compound of the formula I in 60 1 of double-distilled water is sterile-filtered, filled into ampoules, lyophilized under sterile conditions and aseptically sealed. Each ampoule contains 10 mg of active compound.
._.__._....__..... . ,.T_ ......._..__.....___.._,,~""w......~...~,.~ ...."-""--_ "-. _.._....._.___ _......_..._. _.... ...._,.....__..~..._.
._....,...._....__.

Claims

1. A compound of the formula I

in which -A=B-C=D- is a -CH=CH-CH=CH- group in which 1 or 2 CH groups can also be replaced by N, Ar is Ph or naphthyl, which is unsub-stituted or mono-, di- or trisubstituted by H, Hal, Q, alkenyl having up to 6 C
atoms, Ph, OPh, -NO2, NR4R5, NHCOR4, CF3, OCF3, CN, OR4, COOR4, (CH2)n COOR4, (CH2)n NR4R5, -N=C=O or NHCONR4R5, R1, R2 and R3 in each case independently of one another are absent, H, Hal, Q, CF3, NO2, NR4R5, CN, COOR4 or NHCOR4, R4 and R5 in each case independently of one another are H or Q, or together are also -CH2-(CH2)n-CH2-, Q is alkyl having 1 to 6 C atoms, Ph is phenyl, X is O or S, Hal is F, Cl, Br or I, n is 1, 2 or 3, and also their salts, excluding 4-methyl-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-methyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide,~
4-amino-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide and 4-amino-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide.

2. ~5-Bromo-2-ethyl-N-(2,1,3-benzothiadiazol-5-yl)benzene sulfonamide.

3. ~2,5-Dichloro-N-(2,1,3-benzothiadiazol-5-yl)benzene sulfonamide.

4. ~5-Bromo-2-propyl-N-(2,1,3-benzothiadiazol-5-yl)benzene sulfonamide.

5. ~5-Dimethylamino-N-(2,1,3-benzothiadiazol-5-yl)naphthalenesulfonamide.

6. ~5-Dimethylamino-N-[6-methyl-(2,1,3-benzothiadiazol-5-yl)]naphthalenesulfonamide.

7. ~5-Dimenthylamino-N-[4-bromo-(2,1,3-benzothiadiazol-5-yl)]naphthalenesulfonamide.

8. ~5-Dimethylamino-N-(2,1,3-benzothiadiazol-4-yl)naphthalenesulfonamide.

9. ~5-Dimethylamino-N-(1,2,5-oxadiazole-[3,4-b]pyridin-6-yl)naphthalenesulfonamide.

10. ~5-Dimethylamino-N-(1,2,5-benzoxadiazol-5-yl)-1-naphthalenesulfonamide.

11. ~5-Dimethylamino-N-(6-bromo-7-methyl-1,2,5-benzoxadiazol-5-yl)-1-naphthalenesulfonamide.

12. ~2-Phenyl-N-(2,1,3-benzothiadiazol-5-yl)benzene-sulfonamide.

13. ~A process for preparation of a compound according to claim 1 wherein, (a) a compound of the formula II
in which~
-A=B-C=D-, R1, R2, R3 and X have the meanings indicated in claim 1, is reacted with a compound of the formula III

Ar-SO2-E ~III
in which E is Cl, Br, I or a free or reactive functionally modified OH group and Ar has the meaning indicated in claim 1;

(b) for preparation of a compound of the formula I, in which X is S, a compound of the formula IV

in which -A=B-C=D-, Ar, R1, R2 and R3 have the meanings indicated in claim 1, is reacted with thionyl chloride or a reactive derivative of this compound;

or (c) for preparation of a compound of the formula I in which X is O

a compound of the formula V
in which -A=B-C=D-, Ar, R1, R2 and R3 have the meanings indicated in claim 1, is reduced to remove the O- group;
and optionally, one or more of the radicals R1, R2 and R3 are converted into one or more other radicals R1, R2 and R3, respectively, by i) reducing a nitro group to an amino group, ii) replacing a bromo substituent by a cyano group, iii) hydrolysing a cyano group to a carboxyl group, iv) esterifying a carboxyl group, v) converting an amino group by reductive amination into an alkylated amine or vi) acylating an amino group and, optionally converting a base or acid of the formula I
into one of its salts.

14. ~A pharmaceutical composition comprising a compound of formula I as defined in claim 1, or a salt thereof and a pharmaceutically acceptable carrier, diluent or excipient.

15. ~A pharmaceutical composition comprising a compound or salt according to claim 1 or a compound according to any one of claims 2 to 12 and a pharmaceutically acceptable carrier, diluent or excipient.

16. ~A pharmaceutical composition according to claim 14 or 15 for treating an endothelin-dependent disorder in a patient in need of such treating.

17. ~A pharmaceutial composition according to claim 14 or 15 for controlling a cardiac, circulatory or vascular disorder in a patient in need of such controlling.

18. ~A pharmaceutical composition according to claim 16 or 17 comprising a daily dose of 0.02 to 10mg of a compound or salt per kg body weight of the patient.

19. ~A use of a compound or salt of formula I as defined in claim 1, or a compound according to any one of claims 2 to 12 in manufacture of a medicament for treating an endothelin-dependent disorder in a patient in need of such treating.

20. ~A use of a compound or salt of formula I as defined in claim 1 or a compound according to any one of claims 2 to 12 in manufacture of a medicament for controlling a cardiac, circulatory or vascular disorder in a patient in need of such controlling.

21. ~A use according to claim 19 or 20, wherein the compound or salt is in a dosage form adapted for delivery of a daily dose of 0.02 to 10mg of the compound or salt per kg body weight of the patient.

22. ~A use of a compound or salt of formula I as defined in claim 1, or a compound according to any one of claims 2 to 12 for treating an endothelin-dependent disorder in a patient in need of such treating.

23. ~A use of a compound or salt of formula I as defined in claim 1 or a compound according to any one of claims 2 to 12 for controlling a cardiac, circulatory or vascular disorder in a patient in need of such controlling.

24. ~A use according to claim 22 or 23, wherein the compound or salt is in a dosage form adapted for delivery of a daily dose of 0.02 to 10mg of the compound or salt per kg body weight of the patient.

25. ~A compound or salt of formula I as defined in claim 1, or a compound according to any one of claims 2 to 12 for treating an endothelin-dependent disorder in a patient in need of such treating.

26. ~A compound or salt of formula I as defined in claim 1 or a compound according to any one of claims 2 to 12 for controlling a cardiac, circulatory or vascular disorder in a patient in need of such controlling.

27. ~A compound or salt according to claim 25 or 26, wherein the compound or salt is in a dosage form adapted for delivery of a daily dose of 0.02 to 10mg of the compound or salt per kg body weight of the patient.