Substituted anilinic piperidines as MCH selective antagonists

Abstract

This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier.

1 - 9 . (canceled)  
   
   
       10 . A compound having the structure:  
     
       
         
         
             
             
         
       
       wherein R 1  is aryl or heteroaryl optionally substituted with one or more —F, —Cl, —Br, —I, —CN, —NO 2 , —OCH 3 , phenoxy, fused cyclopentanyl, straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl;  
       wherein R 2  is straight-chained or branched C 1 -C 4  alkyl or cyclopropyl;  
       wherein A is —H, —F, —Cl, —Br, —CN, —NO 2 , straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; and  
       wherein n is an integer from 1 to 5 inclusive.  
     
   
   
       11 . The compound of  claim 10 , wherein R 1  is aryl optionally substituted with one or more —F, —Cl, —Br, —I or straight chained or branched C 1 -C 4  alkyl; and 
 wherein A is H.    
   
   
       12 . The compound of  claim 11 , wherein R 2  is isopropyl; and wherein n is 2.  
   
   
       13 . The compound of  claim 12 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       14 . The compound of  claim 12 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       15 . The compound of  claim 12 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       16 . The compound of  claim 10 , wherein R 1  is thienyl; and wherein A is H.  
   
   
       17 - 33 . (canceled)  
   
   
       34 . A compound having the structure:  
     
       
         
         
             
             
         
       
       wherein R 1  is hydrogen, straight chained or branched C 1 -C 7  alkyl, aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more —F, —Cl, —Br, —CN, —NO 2 , —CF 3 , —OCH 3 , straight chained or branched C 1 -C 3  alkyl;  
       wherein R 2  is straight-chained or branched C 3 -C 4  alkyl or cyclopropyl;  
       wherein R 3  is —H, —F, —Cl, —Br, —I, —CN, —NO 2 , —CF 3 , —OCH 3 , or straight chained or branched C 1 -C 3  alkyl, monofluoroalkyl or polyfluoroalkyl, or a phenyl ring fused to C 6  and C 7  of the indole moiety;  
       wherein R 4  is hydrogen or aryl optionally substituted with one or more —F, —Cl, —Br, —I, —CN, —NO 2 , —CF 3 , straight chained or branched C 1 -C 3  alkyl;  
       wherein A is —H, —F, —Cl, —Br, —CN, —NO 2 , straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; and  
       wherein n is an integer from 2 to 4 inclusive.  
     
   
   
       35 . The compound of  claim 34 , wherein R 3  is —H, —F, —Cl, —Br, —I, —CN, —NO 2 , —OCF 3  or —OCH 3 ; and 
 wherein R 4  is hydrogen or phenyl optionally substituted with one or more —F, —Cl or —CF 3 .    
   
   
       36 . The compound of  claim 35 , wherein R 1  is hydrogen or phenyl optionally substituted with one or more —F, —Cl, —Br, —CN, —NO 2 , —CF 3 , —OCH 3  or straight chained or branched C 1 -C 3  alkyl.  
   
   
       37 . The compound of  claim 36 , wherein R 2  is isopropyl.  
   
   
       38 . The compound of  claim 37 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       39 . The compound of  claim 37 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       40 . The compound of  claim 37 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       41 . A compound having the structure:  
     
       
         
         
             
             
         
       
       wherein each R 1  is independently hydrogen or CH 3 ;  
       wherein R 2  is straight-chained or branched C 1 -C 4  alkyl or cyclopropyl;  
       wherein R 3  is benzyl or phenyl, wherein the benzyl or phenyl is optionally substituted with a methylenenedioxy group or one or more —F or —Cl;  
       wherein A is —H, —F, —Cl, —Br, —CN, —NO 2 , straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl;  
       wherein X is (CH 2 ) 2 , COCH 2  or CONH.  
     
   
   
       42 . The compound of  claim 41 , wherein R 3  is phenyl optionally substituted with one or more —F; and 
 wherein A is hydrogen.    
   
   
       43 . The compound of  claim 42 , wherein X is CONH.  
   
   
       44 . The compound of  claim 43 , wherein R 2  is methyl.  
   
   
       45 . The compound of  claim 44 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       46 . The compound of  claim 44 , wherein the compound has the structure:  
     
       
         
         
             
             
         
       
       wherein each Y is independently hydrogen or —F.  
     
   
   
       47 - 79 . (canceled)