Orientation of the oxygen atom at C-6 as a determinant of agonistic activity in the oxymorphone series

AZ Ronai, FF Foldes, EF Hahn and J Fishman

The kinetics of various oxymorphones, their 6-methylene analogs and the 6-hydroxy-epimers corresponding to naloxone and naltrexone have been studied in the longitudinal muscle strip of the guinea-pig ileum. Substitution of the oxygen at C-6 by amethylene group slightly increased antagonistic activity of the resulting structures, without significantly influencing agonistic activity relative to the parent compound. The alpha-orientation of the hydroxy group at C-6 enhanced the agonistic property of both naloxone and naltrexone. The beta- compounds, however, were pure antagonists, with potencies similar to those of the parent keto structures.

Volume 200, Issue 3, pp. 496-500, 03/01/1977
Copyright © 1977 by American Society for Pharmacology and Experimental Therapeutics