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

详细信息    查看全文

• 作者：Gerta Cami-Kobeci ; Willma E. Polgar ; Taline V Khroyan ; Lawrence Toll ; Stephen M. Husbands
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October 13, 2011
• 年：2011
• 卷：54
• 期：19
• 页码：6531-6537
• 全文大小：831K
• 年卷期：v.54,no.19(October 13, 2011)
• ISSN：1520-4804

文摘

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鈥檚 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.