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EP0158775A1 Expired / Lapsed EP ⏱️ 0.0 years remaining

Substituted sulfonamidobenzamides, antiarrythmic agents and compositions thereof

Assignee: Bayer Pharma AG
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Filing: 1985-02-02
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Granted: —
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Expires: 2005-02-02
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Abstract

Abstract Novel substituted sulfonamidobenzamides and their preparation by known methods are described as useful antiarrhythmic agents. Their use in the treatment of cardiac arrhythmias, especially re-entrant arrhythmias, via the prolongation of the action potential of cardiac tissue is provided. Pharmaceutical formulations containing such compounds are also disclosed.

Inventors

  • 👤 David Daniel Davey
  • 👤 William Carl Lumma, Jr.
  • 👤 Ronald André Wohl

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-09 09:42
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/04; C07D295/12; C07D295/125; C07D295/13; A; A61; A61P; A61P9/00; A61P9/06; C07C; C07C255/00

Claims Analysis

Total Claims: 33
Claim 1
Independent Claim 353 words
-1- A compound according to the formula: wherein R = lower alkyl, cycloalkyl, cycloalkyl(lower) alkyl, benzyl, or benzyl substituted by halogen, loweralkyl, loweralkoxy, or lower alkyl substituted by hydroxy, lower alkoxy, carbanoyl, N-loweralkylcarbamoyl, N,N-di- loweralkylcarbamoyl and sulfamoyl; X,X 1 = hydrogen and halogen; R 1 = hydrogen, loweralkyl, unsaturated loweralkyl, loweralkoxyloweralkyl, or collectively with R 2 is an alkylene chain forming an azetidine, pyrrolidine, piperidine, or hexahydroazepine ring, or collectively with R 3 is a bond or an alkylene chain forming an azetidine, pyrrolidine, piperidine or a hexahydroazepine ring, or collectively with R 5 may produce a piperazine or a hexahydro-1,4-diazepine ring system; R 2 = hydrogen, loweralkyl or collectively with R 3 is a bond or an alkylene chain to form a saturated carbocyclic ring of from 4 to 8 ring carbon atoms. R 3 ,R 4 = hydrogen, loweralkyl or collectively is an alkylene chain forming a saturated carbocyclic ring of from 4 to 6 ring carbon atoms; R 5 ,R 6 = hydrogen, loweralkyl, unsaturated loweralkyl, . C 1 -C 12 straight or branched chain alkyl, C 3 -C 6 cycloalkyl, cycloalkyl(lower)alkyl, or when taken together form a saturated heterocyclic ring of from 4 to 8 ring members which may be substituted by one or more methyl groups or optionally contains a -O-, or -S- linkage ↓ O Γ wherein p is the integer 0, 1 or 2; R 6 = loweralkyl substituted by phenyl which may be substituted by up to 3 substituents selected from hydroxy or methoxy groups; n = 0, 1, 2; and the pharmaceutically acceptable salts thereof; with the provisos that: (a) R 5 and R 6 cannot both be hydrogen, ( b ) when either R 5 or R 6 is hydrogen then the other must be C 5 -C 10 straight or branched chain alkyl, cycloalkyl, cycloalkyl lower alkyl or lower alkyl substituted by phenyl which may be substituted by up to 3 substituents selected from hydroxy or methoxy groups. (c) when any or R 1 , R 5 and R 6 is unsaturated loweralkyl, the unsaturation cannot be alpha to the nitrogen atom.
Claim 2
Dependent Claim 9 words
-2-A compound of claim 1 wherein R is loweralkyl.
Claim 3
Dependent Claim 13 words
-3-A compound of claim 1 wherein X and X 1 are both hydrogen.
Claim 4
Dependent Claim 17 words
-4-A compound of claim 1 wherein R 1 ,R 2 ,R 3 and R 4 are hydrogen.
Claim 5
Dependent Claim 21 words
-5-A compound of claim 1 wherein R 5 and R 6 are C 1 -C 12 straight or branched chain alkyl.
Claim 6
Dependent Claim 17 words
-6- A compound of claim 1 wherein R 1 collectively with R 5 produces a piperazine ring.
Claim 7
Dependent Claim 38 words
-7-A compound of claim 1 wherein R is loweralkyl, R 5 and R 6 are C 1 -C 12 straight or branched chain alkyl and X,X 1 ,R 1 ,R 2 ,R 3 and R 4 are hydrogen.
Claim 8
Dependent Claim 34 words
-8-A compound of claim 1 wherein R is loweralkyl, X, X 1 , R 2 , R3, R 4 , R 6 are hydrogen and R 1 with R 5 forms a piperazine ring.
Claim 9
Dependent Claim 8 words
-9-A compound of claim 7 which is N-[2-(diethylamino)-ethyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 10
Dependent Claim 8 words
-10- compound of claim 7 which is N-[3-(diethylamino)-propyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 11
Dependent Claim 9 words
-11-A compound of claim 7 which is 4-[(butylsulfonyl)-amino-N-[2-(diethylamino) ethyl]benzamide.
Claim 12
Dependent Claim 8 words
-12-A compound of claim 7 which is N-[2-(diethylamino)-ethyl]-4-[(ethylsulfonyl)amino]benzamide.
Claim 13
Dependent Claim 8 words
-13-A compound of claim 7 which is N-[4-(diethylamino)-buthyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 14
Dependent Claim 8 words
-14-A compound of claim 7 which is N-[2-(dimethylamino)-ethyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 15
Dependent Claim 9 words
-15- A compound of claim 7 which is N-[2-(dipropylamino)-ethyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 16
Dependent Claim 9 words
-16-A compound of claim 7 which is N-[2-(diisopropyl- amino)ethyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 17
Dependent Claim 8 words
-17-A compound of claim 1 which is (4-[(methylsulfonyl)-amino]-N-[2-(4-morpholinyl)ethyl]benzamide.
Claim 18
Dependent Claim 8 words
-18-A compound of claim 8 which is 4-methyl-l-[4-[(methylsulfonyl)amino]benzoyl]piperazine.
Claim 19
Dependent Claim 7 words
-19-A'compound of claim 1 which is 4-[(methylsulfonyl)-amino]-N-[2-(1-piperidinyl)ethyl]benzamide.
Claim 20
Dependent Claim 9 words
-20- A compound of claim 1 which is 4-[(methylsulfonyl)-amino]-N-[2-(1-pyrrolidinyl)ethyl]benzamide.
Claim 21
Dependent Claim 8 words
-21-A compound of claim 1 which is N-[2-(diethylamino)-ethyl]-N-methyl-4-[(methylsulfonyl)amino]benzamide.
Claim 22
Dependent Claim 8 words
-22-A compound of claim 1 which is 4-[(methylsulfonyl)-amino]-N-[2-(2,2,6,6-tetramethylpiperidino)ethyl]-benzamide.
Claim 23
Dependent Claim 8 words
-23-A compound of claim 1 which is 4-[(methylsulfonyl)-amino]-N-[2-(thionmorpholin-4-yl)ethyl]benzamide.
Claim 24
Dependent Claim 8 words
-24-A compound of claim 1 which is 4-[(methylsulfonyl)-amino]-N-[2-(1-oxothiomorpholin-4-yl)ethyl]benzamide.
Claim 25
Dependent Claim 11 words
-25- A compound of claim 1 which is N-[4-[[2-(diethyl- amino)ethyl]aminocarbonyl]phenyl]benzenemethanesulfon- amide.
Claim 26
Dependent Claim 8 words
-26-A compound of claim 7 which is N-[2-(ethyl(heptyl)-amino)ethyl-4-[(methylsulfonyl)amino]benzamide.
Claim 27
Dependent Claim 9 words
-27-A compound of claim 1 which is trans-N-[2-[(diethyl- amino)cyclohexyl]-4-[(methylsulfonyl)amino)benzamide.
Claim 28
Dependent Claim 10 words
- 2 8-A compound of claim 4 which is N-[2-(diallylamino)-ethyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 29
Dependent Claim 8 words
-29-A compound of claim 1 which is N-allyl-N-[2-(diethylamino)ethyl]-4-[(methylsulfonyl)amino]-benzamide.
Claim 30
Dependent Claim 8 words
-30-A compound of claim 7 which is N-[2-(dibutylamino)-ethyl]-4-[(methylsulfonyl)amino]benzamide.
Claim 31
Dependent Claim 29 words
-31- The method of treating arrhythmias in a mammalian subject in need thereof comprising administering to said subject an antiarrhythmically effective dose of a compound according to claim 1.
Claim 32
Dependent Claim 24 words
-32-A pharmaceutical composition for treating arrhythmias comprising an antiarrhythmic effective amount of a compound of claim 1 together with a non-toxic pharmaceutically acceptable carrier.
Claim 33
Dependent Claim 286 words
- 33 - A process for the preparation of compounds of Formula I comprising activating a substituted nitrobenzoic acid of Formula II (II), wherein X and X 1 are the same or independently hydrogen or halogen, as the acyl halide or ester or acylimidazole or an alkyl chloroformate in an anhydrous aprotic solvent at temperatures from about -50 C to +50°C, preferably at about 0°C, to result in the active intermediate of Formula III (III), wherein Z is halogen, loweralkyl, (R' = loweralkyl) and condensing the thus obtained intermediate of Formula III with an α,ω-diamine of Formula IV (IV), wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 have the meaning given in Formula I, in aprotic solvents at temperatures from about -50°C to +50°C under anhydrous conditions to produce the nitro-benzamide intermediates of Formula V (V), wherein X, X 1 and R 1-6 have the meaning given above, and reducing the intermediate of Formula V by catalytic hydrogenation to produce the amino-benzamide intermediate of Formula VI (VI), wherein X, X 1 and R 1-6 have the meaning given above, and reacting the intermediate of Formula VI with a compound of the formula wherein Z has the meaning given above and R is loweralkyl, cycloalkyl, cycloalkyl (lower) alkyl, benzyl, benzyl substituted by halogen, loweralkyl, loweralkyl, loweralkoxy, or loweralkyl substituted by hydroxy, loweralkoxy, carbamoyl, N-loweralkylcarbamoyl, N,N-diloweralkylcarbamoyl and sulfamoyl, and, if R l is H, reacting the intermediate of Formula V with a compound of the formula ZCHR'OR", wherein Z has the meaning given above and R' is loweralkyl and R" is loweralkyl or loweralkanoyl of 2-5 carbon atoms (straight or branched chain), hydrogenating and sulfonating as indicated above.

References Cited (Backward Citations)

US3162684A Cited
EP0104614A1 Cited

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