Redefining the structure-activity relationships of 2,6-methano-3-benzazocines.: 5.: Opioid receptor binding properties of N-((4'-phenyl)-phenethyl) analogues of 8-CAC

A series of aryl-containing N-monosubstituted analogues of the lead compound 8-[N-((40-phenyl)-phenethyl)]-carboxamidocyclazocine were synthesized and evaluated to probe a putative hydrophobic binding pocket of opioid receptors. Very high binding affinity to the mu opioid receptor was achieved though the N-(2-(4'-methoxybiphenyl-4-yl)ethyl) analogue of 8-CAC. High binding affinity to mu and very high binding affinity to kappa opioid receptors was observed for the N-(3-bromophenethyl) analogue of 8-CAC. High binding a. nity to all three opioid receptors were observed for the N-(2-naphthylethyl) analogue of 8-CAC. (c) 2007 Elsevier Ltd. All rights reserved.