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Structural Determinants of Opioid and NOP Receptor Activity in Derivatives of Buprenorphine

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Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, U.K.
SRI International, Menlo Park, California 94025, United States
Tel: 44 (0)1225 383103. Fax: 44 (0)1225 386114. E-mail: [email protected]
Cite this: J. Med. Chem. 2011, 54, 19, 6531–6537
Publication Date (Web):August 25, 2011
Copyright © 2011 American Chemical Society

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    The unique pharmacological profile of buprenorphine has led to its considerable success as an analgesic and as a treatment agent for drug abuse. Activation of nociceptin/orphanin FQ peptide (NOP) receptors has been postulated to account for certain aspects of buprenorphine’s behavioral profile. In order to investigate the role of NOP activation further, a series of buprenorphine analogues has been synthesized with the aim of increasing affinity for the NOP receptor. Binding and functional assay data on these new compounds indicate that the area around C20 in the orvinols is key to NOP receptor activity, with several compounds displaying higher affinity than buprenorphine. One compound, 1b, was found to be a mu opioid receptor partial agonist of comparable efficacy to buprenorphine but with higher efficacy at NOP receptors.

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    Full experimental details (spectra and microanalysis data) plus figures detailing antagonist activity of 6b in vitro. This material is available free of charge via the Internet at

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