Syntheses and biological evaluation of zwitterionie opioid agonists

ABSTRACT

A series of zwitterionic B-oxymorphine derivatives were synthesized that contain a variety of acyl groups with terminal carboxyl group attached at the 6=NH2 group of B-oxymorphine [1a]. Compounds 1b-d were synthesized by reacting with the appropriate acid anhydride. The aspartic acid derivative le was prepared by reacting la with Bocaspartic acid monobenzyl ester using DCC and HOBt, followed by deprotection with HCI and hydrogenation over Pd/C. The fumaric acid derivative if was synthesized by reacting la with fumaric acid monoethyl ester using DCC and HOBt followed by hydrolysis with NaOH. Reacting oxymorphine [2a] with carboxy-methoxyl-amine gave 2b. Two of the synthesized compounds 1c and 1d were found to be potent reversible agonists as tested in the GPI preparation