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ID: ALA1139291

Journal: Bioorg Med Chem Lett

Title: Syntheses and opioid receptor binding properties of carboxamido-substituted opioids.

Authors: Wentland MP, Lou R, Lu Q, Bu Y, VanAlstine MA, Cohen DJ, Bidlack JM.

Abstract: A series of 15 novel opioid derivatives were made where the prototypic phenolic-OH group of traditional opioids was replaced by a carboxamido (CONH(2)) group. For 2,6-methano-3-benzazocines and morphinans similar or, in a few instances, enhanced affinity for mu, delta and kappa opioid receptors was observed when the OH-->CONH(2) switch was applied. For 4,5alpha-epoxymorphinans, binding affinities for the corresponding carboxamide derivatives were much lower than the OH partner consistent with our pharmacophore hypothesis concerning carboxamide bioactive conformation. The active metabolite of tramadol and its carboxamide counterpart had comparable affinities for the three receptors.

CiteXplore: 19027293

DOI: 10.1016/j.bmcl.2008.10.134