Redefining the structure-activity relationships of 2,6-methano-3- benzazocines. Part 8. High affinity ligands for opioid receptors in the picomolar Ki range: Oxygenated N-(2-[1,1′-biphenyl]-4-ylethyl) analogues of 8-CAC

Abstract

N-[2-(4′-methoxy[1,1′-biphenyl]-4-yl)ethyl]-8-CAC (1) is a high affinity (Ki = 0.084 nM) ligand for the μ opioid receptor and served as the lead compound for this study. Analogues of 1 were made in hopes of identifying an SAR within a series of oxygenated (distal) phenyl derivatives. A number of new analogues were made having single-digit pM affinity for the μ receptor. The most potent was the 3′,4′-methylenedioxy analogue 18 (Ki = 1.6 pM). © 2012 Elsevier Ltd. All rights reserved.