Tertiary amino compounds having opioid receptor affinity

Abstract

Disclosed are compounds of the formula (I) wherein R 1 , R 2 , R 3 R 4 R 5 , R 6 and N are as disclosed herein. The compounds are useful for the treatment of chronic and acute pain.

1 - 7 . (canceled)  
   
   
       8 . A method of treating pain comprising administering to a patient in need thereof, an effective amount of a compound of formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is selected from the group consisting of a bond and C 1-10  alkyl, alkenyl or alkenylene;  
 R 2  and R 3  are independently selected from the group consisting of hydrogen and C 1-10  alkyl, alkenyl or alkenylene;  
 R 4  is selected from the group consisting of a bond and C 1-10  alkyl, alkenyl or alkenylene, said C 1-10  alkyl, alkenyl or alkenylene optionally substituted with 1-3 halogen or oxo groups;  
 R 5  is selected from the group consisting of hydrogen, a 5 or 6 membered aromatic or heteroaromatic group, and a C 3-12  cycloalkyl;  
 R 6  is selected from the group consisting of C 1-10  alkyl, C 3-12  cylcoalkyl and halogen; and  
 N is an integer from 0-3; and pharmaceutically acceptable salts thereof.  
 
   
   
       9 . A method of modulating a pharmacological response from the μ receptor comprising administering an effective amount of a compound of formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is selected from the group consisting of a bond and C 1-10  alkyl, alkenyl or alkenylene;  
 R 2  and R 3  are independently selected from the group consisting of hydrogen and C 1-10  alkyl, alkenyl or alkenylene;  
 R 4  is selected from the group consisting of a bond and C 1-10  alkyl, alkenyl or alkenylene, said C 1-10  alkyl, alkenyl or alkenylene optionally substituted with 1-3 halogen or oxo groups;  
 R 5  is selected from the group consisting of hydrogen, a 5 or 6 membered aromatic or heteroaromatic group, and a C 3-12  cycloalkyl;  
 R 6  is selected from the group consisting of C 1-10  alkyl, C 3-12  cycloalkyl and halogen; and  
 N is an integer from 0-3; and pharmaceutically acceptable salts thereof.  
 
   
   
       10 . A method of reducing side effects associated with the administration of opioid analgesics in a human patient comprising administering to said human patient an analgesically effective amount of a non-opioid compound which exhibits a binding affinity specificity for the μ receptor as compared to the δ 2  receptor (K i  (nM) at the δ 2  receptor/(K i  (nM) at the μ receptor) of greater than about 250.