Novel amines as pharmaceutical agents

Abstract

Novel amines of formulas 1A and 1B are disclosed and are useful as agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, inflammatory diseases, and gastrointestinal disorders, especially IBS. Processes for the preparation and intermediates useful in the preparation are also disclosed.

What is claimed is:  
     
         1 . A compound of the formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof wherein: 
 n is an integer of from 0 to 2;  
 R is sulfonamide, 
 amide,  
 phosphonic acid,  
 heterocycle,  
 sulfonic acid, or  
 hydroxamic acid;  
 
 A is hydrogen or methyl; and  
 B is  
                     straight or branched alkyl of from 1 to 11 carbons, or    —(CH 2 ) 1-4 —Y—(CH 2 ) 0-4 -phenyl wherein Y is —O—, —S—, —NR′ 3  
 wherein R′ 3  is alkyl of from 1 to 6 carbons, cycloalkyl of from 3 to 8 carbons, benzyl or phenyl wherein benzyl or phenyl can be unsubstituted or substituted with from 1 to 3 substituents each independently selected from alkyl, alkoxy, halogen, hydroxy, carboxy, carboalkoxy, trifluoromethyl, and nitro,  
   
 provided that when A is hydrogen, B is not isobutyl.  
 
     
     
         2 . A compound of the formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof wherein: 
 n is an integer of from 0 to 2; and  
 R is sulfonamide, 
 amide,  
 phosphonic acid,  
 heterocycle,  
 sulfonic acid, or  
 hydroxamic acid,  
 
 provided that when R is heterocycle, the heterocycle is not  
                     
 
     
     
         3 . A compound according to  claim 1  wherein n is 1 and R is  
       
         
           
           
               
               
           
         
       
     
     
         4 . A compound according to  claim 1  wherein R is a sulfonamide selected from —NHSO 2 R 15  or —SO 2 NHR 15  wherein R 15  is straight or branched alkyl or trifluoromethyl.  
     
     
         5 . A compound according to  claim 2  wherein R is a sulfonamide selected from —NHSO 2 R 15  or —SO 2 NHR 15  wherein R 15  is straight or branched alkyl or trifluoromethyl.  
     
     
         6 . A compound according to  claim 1  named: 
 3-(3-Amino-2-cyclopentyl-propyl)-4H-[1,2,4]oxadiazol-5-one;  
 3-(3-Amino-2-cyclopentyl-propyl)-4H-[1,2,4]thiadiazol-5-one;  
 2-Cyclopentyl-3-(2-oxo-2,3-dihydro-2λ 4 -[1,2,3,5]oxathiadiazol-4-yl)-propylamine;  
 3-(3-Amino-2-cyclobutyl-propyl)-4H-[1,2,4]oxadiazol-5-one;  
 3-(3-Amino-2-cyclobutyl-propyl)-4H-[1,2,4]thiadiazol-5-one; and  
 2-Cyclobutyl-3-(2-oxo-2,3-dihydro-2λ 4 -[1,2,3,5]oxathiadiazol-4-yl)-propylamine.  
 
     
     
         7 . A compound according to  claim 2  named: 
 (2-Aminomethyl-4-methyl-pentyl)-phosphonic acid.  
 
     
     
         8 . A compound according to  claim 1  wherein R is a phosphonic acid, —PO 3 H 2 .  
     
     
         9 . A compound according to  claim 2  wherein R is a phosphonic acid, —PO 3 H 2 .  
     
     
         10 . A compound according to  claim 1  wherein R is a heterocycle selected from  
       
         
           
           
               
               
           
         
       
     
     
         11 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         12 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 2  and a pharmaceutically acceptable carrier.  
     
     
         13 . A method for treating epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, gastrointestinal damage, inflammation or gastrointestinal disorders comprising administering a therapeutically effective amount of a compound according to  claim 1  to a mammal in need of said treatment.  
     
     
         14 . A method for treating epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, gastrointestinal damage, inflammation or gastrointestinal disorders comprising administering a therapeutically effective amount of a compound according to  claim 2  to a mammal in need of said treatment.  
     
     
         15 . A method according to  claim 13  wherein the gastrointestinal disorder is irritable bowel syndrome.  
     
     
         16 . A method according to  claim 14  wherein the gastrointestinal disorder is irritable bowel syndrome.