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

doi:10.1016/j.bmcl.2007.09.082

Bioorganic & Medicinal Chemistry Letters

Volume 17, Issue 23, 1 December 2007, Pages 6516-6520

https://doi.org/10.1016/j.bmcl.2007.09.082 Get rights and content

Abstract

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.

Graphical abstract

Novel analogues of 8-carboxamidocyclazocine have very high affinity for opioid receptors.

Section snippets

Acknowledgments

We gratefully acknowledge the contributions of Rensselaer’s mass spectroscopist Dr. Dmitri Zagorevski and the technical assistance provided by Brian I. Knapp of the University of Rochester. Funding of this research was from NIDA (DA12180 and KO5-DA00360) and the NSF (Agilent 1100 series LC/MSD system).

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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

Abstract

Graphical abstract

Section snippets

Acknowledgments

Bioorgan. Med. Chem. Lett.

J. Med. Chem.

J. Pharmacol. Exp. Ther.

Neurochem. Res.