Large substitutent, non-phenolic opioids and methods of use thereof

Abstract

8-Substituted-2,6-methano-3-benzazocines of general structure are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

I claim: 
     
         1 . A compound of formula: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein
 Q is 
 
       
       
         
           
           
               
               
           
         
         
           A is (CH 2 ) n , wherein one or more CH 2  may be replaced by —O—, cycloalkyl or CR 1a R 1b ; 
           R 1a  and R 1b  are chosen independently from hydrogen, halogen, lower alkyl, lower alkoxy and lower alkylthio; 
         
       
       
         
           
           
               
               
           
         
       
       is an aryl or heteroaryl residue of one to three rings;
   R 10  is one or two residues chosen independently from hydrogen, hydroxyl, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy and (C 1 -C 6 )alkylthio;   
 R 11  is H or 
 
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       is an aryl or heteroaryl residue of one to three rings;
   A′ is (CH 2 ) m  wherein one or more CH 2  may be replaced by —O—, cycloalkyl, —CR 1a R 1b , —C(═O)— or —NH—;   R 12  is chosen from hydrogen and lower alkyl;   R 15  is one or two residues chosen independently from hydrogen, hydroxyl, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy and (C 1 -C 6 )alkylthio;   m is zero or an integer from 1 to 6; and   n is an integer from 1 to 6.   
 
     
     
         2 . A method of treating a patient suffering from a disease or condition wherein said disease or condition is chosen from the group consisting of pain, pruritis, diarrhea, irritable bowel syndrome, gastrointestinal motility disorder, obesity, respiratory depression, convulsions, coughing, hyperalgesia, dyskinesia and drug addiction comprising administering to said patient a compound of  claim 1  or a pharmaceutically acceptable salt thereof.