Structural Determinants of Opioid and NOP Receptor Activity in Derivatives of Buprenorphine
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 o...
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| Veröffentlicht in: | Journal of medicinal chemistry 2011-10, Vol.54 (19), p.6531-6537 |
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| container_end_page | 6537 |
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| container_issue | 19 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 54 |
| creator | Cami-Kobeci, Gerta Polgar, Willma E Khroyan, Taline V Toll, Lawrence Husbands, Stephen M |
| description | 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. |
| doi_str_mv | 10.1021/jm2003238 |
| format | Article |
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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. 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Med. Chem</addtitle><description>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. 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| ispartof | Journal of medicinal chemistry, 2011-10, Vol.54 (19), p.6531-6537 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Buprenorphine - analogs & derivatives Buprenorphine - chemical synthesis Buprenorphine - pharmacology CHO Cells Cricetinae Cricetulus Drug Partial Agonism Humans Ligands Models, Molecular Radioligand Assay Receptors, Opioid - metabolism Receptors, Opioid, delta - metabolism Receptors, Opioid, kappa - metabolism Receptors, Opioid, mu - agonists Receptors, Opioid, mu - metabolism Stereoisomerism Structure-Activity Relationship |
| title | Structural Determinants of Opioid and NOP Receptor Activity in Derivatives of Buprenorphine |
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