Stereochemical studies on medicinal agents. 23. Synthesis and biological evaluation of 6-amino derivatives of naloxone and naltrexone

Abstract

Epimeric 6-amino derivatives of naloxone and naltrexone were synthesized, and the configuration at the C-6 chiral center was determined from NMR studies. All derivatives possessed narcotic antagonist activity in mice, with each of the 6.beta. epimers having greater potency than the corresponding 6.alpha. epimers. The affinities of these epimers in vitro paralled their in vivo potencies. Slight antinociceptic properties were observed with 3 of the 4 compounds. The naloxone derivatives were suggested as long-acting narcotic antagonists in the treatment of human narcotic addiction because of their 4-fold greater duration of action relative to the other antagonists.