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 |
| Early online date | 24 Aug 2011 |
| DOIs | |
| Publication status | Published - 13 Oct 2011 |
Access to Document
- Husbands_JMC_2011_54_19_6531.pdf
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm2003238