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-((4′-phenyl)-phenethyl)]-carboxamidocyclazocine were synthesized and evaluated to probe a putative hydrophobic binding pocket of opioid receptors. Very high binding affinity to the μ opioid receptor was achieved though the N-(2-(4′-methoxybiphenyl-4-yl)ethyl) analogue of 8-CAC. High binding affinity to μ and very high binding affinity to κ opioid receptors was observed for the N-(3-bromophenethyl) analogue of 8-CAC. High binding affinity to all three opioid receptors were observed for the N-(2-naphthylethyl) analogue of 8-CAC.