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

N-[2-(4'-methoxy[1,1'-biphenyl]-4-yl) ethyl]-8-CAC (1) is a high affinity (K-i = 0.084 nM) ligand for the mu 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 l receptor. The most potent was the 3',4'-methylenedioxy analogue 18 (K-i = 1.6 pM). (C) 2012 Elsevier Ltd. All rights reserved.