Substituted alkyl amido piperidines

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. This invention also provides a method of reducing the body mass of a subject which comprises administering to the subject an amount of a compound of the invention effective to reduce the body mass of the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety.

1 - 38 . (canceled)  
     
     
         39 . A method of treating a subject suffering from depression comprising administering to the subject a therapeutically effective amount of a compound having the structure:  
       
         
           
           
               
               
           
         
         wherein each R 1  is independently hydrogen; —F; —Cl; —Br; —I; —CN; —NO 2 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl; C 3 -C 7  cycloalkyl or C 5 -C 7  cycloalkenyl; aryl; heteroaryl; —N(R 5 ) 2 ; —(CH 2 ) m OR 5 ; —COR 5 ; —CO 2 R 5 ; —OCOR 5 ; —CON(R 5 ) 2 ; —N(R 5 )COR 5 ; —N(R 5 )CON(R 5 ) 2 ; —OCON(R 5 ) 2  or —N(R 5 )CO 2 R 5 ;  
         wherein R 2  is hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; —NH 2 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1    
         wherein R 3  is hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1 ; or wherein R 2  and R 3  together can be —(CH 2 ) p —;  
         wherein R 4  is straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl, C 3 -C 6  cycloalkyl, C 1 -C 7  alkyl-C 3 -C 6  cycloalkyl; —N(R 5 ) 2  or —(CH 2 ) m OR 5 ;  
         wherein each R 5  is independently hydrogen; aryl; heteroaryl or straight chained or branched C 1 -C 7  alkyl, wherein the alkyl may be substituted with an aryl or heteroaryl;  
         wherein each R 6  is independently hydrogen; straight chained or branched C 1 -C 7  alkyl;  
         wherein each R 7  is independently hydrogen; phenyl or straight chained or branched C 1 -C 7  alkyl, wherein the alkyl may be substituted with a phenyl;  
         wherein each m is independently an integer from 0 to 5 inclusive;  
         wherein n is an integer from 1 to 5 inclusive;  
         wherein p is an integer from 2 to 7 inclusive;  
         wherein q is an integer from 0 to 2 inclusive; and  
         wherein each X is independently CR 1  or N, provided that if one X is N then the remaining X are CR 1 ;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         40 . The method of  claim 39 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         41 . The method of  claim 40 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
         wherein R 2  and R 3  are each independently hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1 ; or wherein R 2  and R 3  together can be —(CH 2 ) p —;  
         wherein R 4  is straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl, C 3 -C 6  cycloalkyl, —N(R 5 ) 2  or —(CH 2 ) m OR 5 ; and X is CH or N.  
       
     
     
         42 . The method of  claim 41 , wherein X is CH.  
     
     
         43 . The method of  claim 41 , wherein X is N.  
     
     
         44 . A method of treating a subject suffering from anxiety comprising administering to the subject a therapeutically effective amount of a compound having the structure:  
       
         
           
           
               
               
           
         
         wherein each R 1  is independently hydrogen; —F; —Cl; —Br; —I; —CN; —NO 2 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl; C 3 -C 7  cycloalkyl or C 5 -C 7  cycloalkenyl; aryl; heteroaryl; —N(R 5 ) 2 ; —(CH 2 ) m OR 5 ; —COR 5 ; —CO 2 R 5 ; —OCOR 5 ; —CON(R 5 ) 2 ; —N(R 5 )COR 5 ; —N(R 5 )CON(R 5 ) 2 ; —OCON(R 5 ) 2  or —N(R 5 )CO 2 R 5 ;  
         wherein R 2  is hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; —NH 2 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1    
         wherein R 3  is hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1 ; or wherein R 2  and R 3  together can be —(CH 2 ) p —;  
         wherein R 4  is straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl, C 3 -C 6  cycloalkyl, C 1 -C 7  alkyl-C 3 -C 6  cycloalkyl; —N(R 5 ) 2  or —(CH 2 ) m OR 5 ;  
         wherein each R 5  is independently hydrogen; aryl; heteroaryl or straight chained or branched C 1 -C 7  alkyl, wherein the alkyl may be substituted with an aryl or heteroaryl;  
         wherein each R 6  is independently hydrogen; straight chained or branched C 1 -C 7  alkyl;  
         wherein each R 7  is independently hydrogen; phenyl or straight chained or branched C 1 -C 7  alkyl, wherein the alkyl may be substituted with a phenyl;  
         wherein each m is independently an integer from 0 to 5 inclusive;  
         wherein n is an integer from 1 to 5 inclusive;  
         wherein p is an integer from 2 to 7 inclusive;  
         wherein q is an integer from 0 to 2 inclusive; and  
         wherein each X is independently CR 1  or N, provided that if one X is N then the remaining X are CR 1 ;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         45 . The method of  claim 44 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         46 . The method of  claim 45 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
         wherein R 2  and R 3  are each independently hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1 ; or wherein R 2  and R 3  together can be —(CH 2 ) p —;  
         wherein R 4  is straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl, C 3 -C 6  cycloalkyl, —N(R 5 ) 2  or —(CH 2 ) m OR 5 ; and X is CH or N.  
       
     
     
         47 . The method of  claim 46 , wherein X is CH.  
     
     
         48 . The method of  claim 46 , wherein X is N.  
     
     
         49 . A method of treating a subject suffering from obesity comprising administering to the subject a therapeutically effective amount of a compound having the structure:  
       
         
           
           
               
               
           
         
         wherein each R 1  is independently hydrogen; —F; —Cl; —Br; —I; —CN; —NO 2 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl; C 3 -C 7  cycloalkyl or C 5 -C 7  cycloalkenyl; aryl; heteroaryl; —N(R 5 ) 2 ; —(CH 2 ) m OR 5 ; —COR 5 ; —CO 2 R 5 ; —OCOR 5 ; —CON(R 5 ) 2 ; —N(R 5 )COR 5 ; —N(R 5 )CON(R 5 ) 2 ; —OCON(R 5 ) 2  or —N(R 5 )CO 2 R 5 ;  
         wherein R 2  is hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; —NH 2 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1    
         wherein R 3  is hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1 ; or wherein R 2  and R 3  together can be —(CH 2 ) p —;  
         wherein R 4  is straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl, C 3 -C 6  cycloalkyl, C 1 -C 7  alkyl-C 3 -C 6  cycloalkyl; —N(R 5 ) 2  or —(CH 2 ) m OR 5 ;  
         wherein each R 5  is independently hydrogen; aryl; heteroaryl or straight chained or branched C 1 -C 7  alkyl, wherein the alkyl may be substituted with an aryl or heteroaryl;  
         wherein each R 6  is independently hydrogen; straight chained or branched C 1 -C 7  alkyl;  
         wherein each R 7  is independently hydrogen; phenyl or straight chained or branched C 1 -C 7  alkyl, wherein the alkyl may be substituted with a phenyl;  
         wherein each m is independently an integer from 0 to 5 inclusive;  
         wherein n is an integer from 1 to 5 inclusive;  
         wherein p is an integer from 2 to 7 inclusive;  
         wherein q is an integer from 0 to 2 inclusive; and  
         wherein each X is independently CR 1  or N, provided that if one X is N then the remaining X are CR 1 ;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         50 . The method of  claim 49 , where the compound has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         51 . The method of  claim 50 , wherein the compound has the structure:  
       
         
           
           
               
               
           
         
         wherein R 2  and R 3  are each independently hydrogen; —F; —Cl; —Br; —I; —CN; —(CH 2 ) m OR 5 ; —(CH 2 ) m SR 5 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more R 1 ; or wherein R 2  and R 3  together can be —(CH 2 ) p —;  
         wherein R 4  is straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl, C 3 -C 6  cycloalkyl, —N(R 5 ) 2  or —(CH 2 ) m OR 5 ; and X is CH or N.  
       
     
     
         52 . The method of  claim 51 , wherein X is CH.  
     
     
         53 . The method of  claim 51 , wherein X is N.