Benzoic acid derivatives and related compounds as antiarrhythmic agents

Abstract

Benzoic acid derivatives of the formula I where X is oxygen, sulfur, —NH, —NR 1 , —N—CN, —N—OR 1 or —N—NO 2 ; Y is a single bond, —C═C—, or —NH; R 1 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclo, or (heterocyclo)alkyl; and R 2 is aryl or heterocyclo. The compounds of formula I are useful in the treatment of arrhythmia.

What is claimed is:  
     
         1 . A method of treating cardiac arrhythmia which comprises administering to a mammal in need thereof an effective amount of a compound of the formula I  
       
         
           
           
               
               
           
         
       
       where 
 X is oxygen, sulfur, —NH, —NR 1 , —N—CN, —N—OR 1  or —N—NO 2 ;  
 Y is a single bond, —C═C—, or —NH;  
 R 1  is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclo, or (heterocyclo)alkyl; and  
 R 2  is aryl or heterocyclo.  
 
     
     
         2 . A compound of the formula I  
       
         
           
           
               
               
           
         
       
       where 
 X is oxygen, sulfur, —NH, —NR 1 , —N—CN, —N—OR 1  or —N—NO 2 ;  
 Y is a single bond, —C═C—, or —NH;  
 R 1  is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclo, or (heterocyclo)alkyl; and  
 R 2  is aryl or heterocyclo.  
 
     
     
         3 . A compound as recited in  claim 2  wherein 
 X is oxygen or N—CN;  
 Y is a single bond or NH; and  
 R 1  is alkyl, cycloalkyl, (aryl)alkyl, (cycloalkyl)alkyl, or (substituted-amino)alkyl.  
 
     
     
         4 . A compound as recited in  claim 2  wherein 
 X is oxygen;  
 Y is a single bond or NH; and  
 R 1  is alkyl, cycloalkyl, (aryl)alkyl, (cycloalkyl)alkyl, or (substituted-amino)alkyl.  
 
     
     
         5 . A compound as recited in  claim 2  wherein 
 X is N—CN;  
 Y is a single bond or NH; and  
 R 1  is alkyl, cycloalkyl, (aryl)alkyl, (cycloalkyl)alkyl, or (substituted-amino)alkyl.  
 
     
     
         6 . A compound as recited in  claim 2  wherein 
 X is oxygen or N—CN;  
 Y is NH; and  
 R 1  is alkyl, cycloalkyl, (aryl)alkyl, (cycloalkyl)alkyl, or (substituted-amino)alkyl.  
 
     
     
         7 . A compound as recited in  claim 2  wherein 
 X is oxygen;  
 Y is a single bond; and  
 R 1  is alkyl, cycloalkyl, (aryl)alkyl, (cycloalkyl)alkyl, or (substituted-amino)alkyl.  
 
     
     
         8 . A compound as recited in  claim 2  wherein 
 X is N—CN  
 Y is a single bond; and  
 R 1  is alkyl, cycloalkyl, (aryl)alkyl, (cycloalkyl)alkyl, or (substituted-amino)alkyl.  
 
     
     
         9 . A compound as recited in  claim 2  wherein 
 X is oxygen or N—CN;  
 Y is single bond or NH; and  
 R 1  is alkyl.  
 
     
     
         10 . A compound as recited in  claim 2  wherein 
 X is oxygen or N—CN;  
 Y is single bond or NH and  
 R 1  is cycloalkyl.  
 
     
     
         11 . A compound as recited in  claim 2  wherein 
 X is N—CN;  
 Y is single bond or NH; and  
 R 1  is (aryl)alkyl.  
 
     
     
         12 . A compound as recited in  claim 2  wherein 
 X is N—CN;  
 Y is single bond or NH; and  
 R 1  is (cycloalkyl)alkyl.  
 
     
     
         13 . A compound as recited in  claim 2  wherein 
 X is N—CN;  
 Y is single bond or NH and  
 R 1  is (substituted-amino)alkyl.  
 
     
     
         14 . A compound as recited in  claim 2  which is: 
 (+)-N-[(2,2-dimethylcyclopentyl)methyl]-4-hexyloxybenzamide and (−)-N-[(2,2-dimethylcyclopentyl)-methyl]-4-hexyloxybenzamide;  
 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-dimethylbutyl)-2-(hexyloxy)-5-pyridine carboxamide;  
 N-(3,3-dimethylbutyl)-1-hexyl-1,2-dihydro-2-oxo-5-pyridinecarboxamide;  
 N-cyano-N′-(3,3-dimethylbutyl)-6-(hexyloxy)benzene-carboximidamide;  
 N-(3,3-dimethylbutyl)-N′-[4-(hexyloxy)phenyl]urea;  
 N-(3, 3-dimethylbutyl)-N′-[4-(hexyloxy)phenyl]urea;  
 or a compound of  claim 2  having the structure;