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US 6,624,309 B1Granted
Benzoic acid derivatives and related compounds as antiarrhythmic agents
AssigneeBristol-Myers Squibb Company
InventorsJohn Lloyd, George C. Rovnyak, Philip D. Stein, Saleem Ahmad, Karnail S. Atwal, Thomas J. Caulfield, Michael A. Poss
Life of this patent
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Abstract
Benzoic acid derivatives of the formula where X is oxygen, sulfur, —NH, —NR1, —N—CN, —N—OR1 or —N—NO2; Y is a single bond, —C═C—, or —NH; R1 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclo, or (heterocyclo)alkyl; and R2 is aryl or heterocyclo. The compounds of formula I are useful in the treatment of arrhythmia.
Claims6
A method of treating cardiac arrhythmia which comprises administering to a mammal in need thereof an effective amount of a compound of the formula
- where
- X is oxygen;
- Y is a single bond;
- R1 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, (aryl)alkyl or (cycloalkyl)alkyl;
- and
- R2 is aryl which cannot be substituted with OH or a phenolic ester group and must be substituted with a heterocyclo group at the 4-position which is a fully saturated or unsaturated ring of five or six atoms containing one or two oxygen and/or sulfur atoms and/or one to four nitrogen atoms provided that the total number of hetero atoms in the ring is four or less, or the heterocyclic group is a bicyclic ring wherein the five or six-membered ring containing oxygen and/or sulfur and/or nitrogen atoms as defined above is fused to a benzene ring;
- with the proviso that
- (1) the heterocyclo group substituted on the R2 aryl is exclusive of
- where X1 is —CRaRb— and Y1 is O, S or —NRc— where Ra, Rb, and Rc, which may be the same or different, are independently H or C1-4alkyl;
- (2) R1 is exclusive of aminoalkyl;
- (3) where R1 is cycloalkyl or (cycloalkyl)alkyl, the cycloalkyl group is unsubstituted or is substituted with alkyl or hydroxy, where the alkyl is unsubstituted or is substituted with halo, alkoxy, aryl, cycloalkyl, hydroxy, nitro, cyano, thiol or alkylthio;
- and
- (4) where R1 is aryl, then the heterocyclic group substituted on the R2 aryl is exclusive of
- where Rd is H or alkyl.
11 more elements
A compound of the formula
- wherein the above oxadiazolyl ring is optionally substituted with alkyl, aryl, alkylthio, alkoxy, halo, nitro, keto, cyano, hydroxy, azo, oxo, thiazo, amino, substituted amino, carboxylic acid, carboxylic ester, or alkoxy further substituted with a carboxylic acid or a five- to eight-membered ring optionally containing 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur, optionally substituted by alkyl or halogen;
- and R1 is (cycloalkyl)alkyl, or a pharmaceutically acceptable salt thereof;
- with the proviso that in the R1 (cycloalkyl)alkyl, the cycloalkyl group is unsubstituted or is substituted with alkyl or hydroxy, where the alkyl is unsubstituted or is substituted with halo, alkoxy, aryl, cycloalkyl, hydroxy, nitro, cyano, thiol or alkylthio.
A compound which is:
- N-(3,3-dimethylbutyl)-4-(1H-indol-1-yl)benzamide;
- 4-(3-butyl-1,2,4-oxadiazol-5-yl)-N-(3, 3-dimethylbutyl)-benzamide;
- N-(3,3-dimethylcyclopentyl)-4-(1H-indol-1-yl)benzamide;
- or a pharmaceutically acceptable salt thereof.
1 more element
Dependencies are inferred from the claim text.