X-RAY CRYSTAL-STRUCTURES OF POTENT OPIOID RECEPTOR LIGANDS - ETONITAZENE, CIS-(-3-METHYLFENTANYL, ETORPHINE, DIPRENORPHINE, AND BUPRENORPHINE())

As a prelude to molecular modeling and other studies of the newly clon ed and expressed mu, delta and kappa opioid receptor subtypes, X-Ray c rystal structures were determined for etonitazene, (1) cis-(+)-3-methy lfentanyl (4) and etorphine (6), three extremely potent opioid agonist s. X-Ray crystal structures were also determined for diprenorphine 7, a potent opioid antagonist, and buprenorphine (8), a clinically useful mixed agonist-antagonist. Agonists (1), (4) and (6) are structurally diverse but have similar profiles while (7) and (8) have substantially different pharmacological profiles but differ structurally by only a methyl vs. a tertbutyl function. The present results should facilitate studies toward understanding the differences which underlie these obs ervations on a molecular basis.