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ID: ALA1795257

Journal: Bioorg Med Chem Lett

Title: Synthesis of new opioid derivatives with a propellane skeleton and their pharmacology: part 1.

Authors: Yamamoto N, Fujii H, Nemoto T, Nakajima R, Momen S, Izumimoto N, Hasebe K, Mochizuki H, Nagase H.

Abstract: The observation that 17-cyclopropylmethylmorphinan derivatives without the 4,5-epoxy ring showed more κ selectivity than those with a 4,5-epoxy ring led us to develop a working hypothesis: the position of the plane composed of the A and B rings would influence the opioid receptor type selectivity and that the decrease in the torsion angle C11-C12-C13-C14 could improve the κ selectivity. Consistent with our hypothesis, KNT-42 with an N-cyclopropylmethyl propellane structure, whose A and B rings were fixed in a torsion angle of approximately 0°, showed κ selective agonist activity.

CiteXplore: 21641798

DOI: 10.1016/j.bmcl.2011.04.147