Method for decreasing opioid metabolism

Abstract

8-Substituted-2,6-methano-3-benzazocines of general streucture I in which A is —CH 2 —OH, —CH 2 NH 2 , —NHSO 2 CH 3 , and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.

1 - 31 . (canceled)  
     
     
         32 . A method for treating a disease or condition by altering a response mediated by an opioid receptor comprising bringing into contact with said opioid receptor a compound having the formula  
       
         
           
           
               
               
           
         
       
       wherein 
 A is chosen from —CH 2 -Z, —NHSO 2 -(loweralkyl),  
                     
 Q is chosen from O, S and NR 17 ;  
 Y is chosen from O, S, NR 17  and NOH;  
 Z is chosen from OH, SH and NH 2 ;  
 R 1  is chosen from hydrogen, lower alkoxy, phenyl and —NHR 8 ;  
 R 8  is chosen from hydrogen, —OH, —NH 2  and —CH 2 R 15 ;  
 R 15  is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino;  
 R 16  is chosen from hydrogen and NH 2 ; and  
 R 17  is chosen from hydrogen, alkyl, aryl and benzyl; and  
 B represents an appropriate residue such that an existing compound  
                     
 alters a response mediated by said opioid receptor with the proviso that said existing compound cannot be: (a) cyclazocine converted to —NHCHO; (b) naltrexone or oxymorphone converted to —NHSO 2 CH 3 ; (c) levo-methylmorphinan converted to levo-(methylmorphinan-3-yl)phenylmethanone; or (d) dextro N-benzylnormetazocine converted to dextro N-[1-benzyl-6,11-dimethylbenzomorphan-8-yl] methanesulfonamide.  
 
     
     
         33 . A method according to claim  31  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 and drug addiction.  
     
     
         34 - 50 . (canceled)  
     
     
         51 . A method according to claim  31  wherein A is chosen from the group consisting of: —COOCH 3 , -COOEt, —CONH 2 , —C(═S)NH 2 , —C(O)NHOH, —C(O)NHNH 2 , —CONHCH 3 , -CONHBn, —CONHCH 2 (4-MeOC 6 H 4 ), 2-(4,5-dihydroimidazolyl), —C(═NOH)NH 2 , —CH 2 NH 2 , CH 2 OH, —COC 6 H 5 , —CN, —C(═NOH)C 6 H 5 , —NHCHO, —NHCHS and —NHSO 2 CH 3 .  
     
     
         52 . A method according to  claim 51  wherein A is chosen from the group consisting of: —CONH 2 , —C(═S)NH 2 , —C(═NOH)NH 2 , and —NHCHO.  
     
     
         53 . A method according to  claim 33  wherein said disease or condition is obesity or drug addiction.  
     
     
         54 . A method according to  claim 53  wherein said drug addiction is chosen from alcohol addiction, nicotine addiction, cocaine addiction and heroin addiction.