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

Mark P Wentland, Rongliang Lou, Qun Lu, Yigong Bu, Melissa A VanAlstine, Dana J Cohen, Jean M Bidlack

Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wentmp@rpi.edu

Bioorganic & medicinal chemistry letters 2009 Jan 1

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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.

Citation

Mark P Wentland, Rongliang Lou, Qun Lu, Yigong Bu, Melissa A VanAlstine, Dana J Cohen, Jean M Bidlack. Syntheses and opioid receptor binding properties of carboxamido-substituted opioids. Bioorganic & medicinal chemistry letters. 2009 Jan 1;19(1):203-8