Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine

Gerta Cami-Kobeci; Willma E. Polgar; Taline V. Khroyan; Lawrence Toll; Stephen M. Husbands

doi:10.1021/jm2003238

Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine

Gerta Cami-Kobeci, Willma E. Polgar, Taline V. Khroyan, Lawrence Toll, Stephen M. Husbands

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	6531-6537
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	54
Issue number	19
DOIs	https://doi.org/10.1021/jm2003238
Publication status	E-pub ahead of print - 25 Aug 2011

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AU - Husbands, Stephen M.

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Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine

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