Bicyclic heterocycles as cannabinoid receptor modulators

Abstract

The present application describes compounds according to Formula I, pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents and methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents. The compounds have the general Formula I: including all prodrugs, pharmaceutically acceptable salts and stereoisomers, R 1 , R 2 , R 3 , n, and Z are described herein.

1 . A compound or a pharmaceutically acceptable salt or a stereoisomer according to Formula I:  
       
         
           
           
               
               
           
         
       
       wherein, 
 Z is selected from the group consisting of a direct bond, oxygen, N(R 4 ) and alkyl;  
 R 1  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, halo, CF 3 , CN;  
 R 2  is selected from the group consisting of cycloalkyl, aryl and heteroaryl;  
 R 3  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkoxy and heteroarylalkyl;  
 R 4  is selected from the group consisting of hydrogen, alkyl; wherein R 3  and R 4  may be taken together to form a heterocyclyl; and  
 n is an integer of 0 or 1.  
 
     
     
         2 . The compound according to  claim 1  wherein, 
 n is 1.    
     
     
         3 . The compound according to  claim 2  wherein, 
 R 2  is selected from the group consisting of aryl and heteroaryl.    
     
     
         4 . The compound according to  claim 3  wherein, 
 R 1  is selected from the group consisting of aryl, heteroaryl, CF 3  and CN.    
     
     
         5 . The compound according to  claim 4  wherein, 
 R 1  is aryl.    
     
     
         6 . The compound according to  claim 4  wherein, 
 R 1  is CN.    
     
     
         7 . The compound according to  claim 3  wherein, 
 R 3  is selected from the group consisting of cycloalkyl, cycloalkylalkyl, heterocyclyl and arylalkyl.    
     
     
         8 . The compound according to  claim 1  wherein the compound is selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         9 . A pharmaceutical composition, comprising: 
 at least one compound according to  claim 1;  and    at least one pharmaceutically acceptable diluent or carrier.    
     
     
         10 . The pharmaceutical composition according to  claim 9 , further comprising: 
 at least one additional therapeutic agent.    
     
     
         11 . A method for treating obesity, comprising administering to a patient in need a therapeutically effective amount of a cannabinoid receptor 1 (CB1) antagonist or inverse agonist according to  claim 1 .  
     
     
         12 . A method for smoking cessation, comprising administering to a patient in need a therapeutically effective amount of a cannabinoid receptor 1 (CB1) antagonist or inverse agonist according to  claim 1.