|
|||||
|
|
Structure-activity studies of a novel series of isoxazole-3-carboxamide derivatives as TRPV1 antagonists |
|
| Authors: | Palin Ronald Abernethy Lynn Ansari Nasrin Cameron Kenneth Clarkson Tom Dempster Maureen Dunn David Easson Anna-Marie Edwards Darren Maclean John Everett Katy Feilden Helen Ho Koc-Kan Kultgen Steve Littlewood Peter McArthur Duncan McGregor Deborah McLuskey Hazel Neagu Irina Neale Stuart Nisbet Lesley-Anne Ohlmeyer Michael Pham Quynhchi Ratcliffe Paul Rong Yajing Roughton Andrew Sammons Melanie Swanson Robert Tracey Heather Walker Glenn |
| Affiliation: | a Department of Chemistry, MSD, Newhouse, Lanarkshire ML1 5SH, UK b Department of Pharmacology, MSD, Newhouse, Lanarkshire ML1 5SH, UK c Department of Molecular Pharmacology, MSD, Newhouse, Lanarkshire ML1 5SH, UK d Pharmacopeia, PO Box 5350, Princeton, NJ, 08543, United States |
| Abstract: | Optimisation of a screening hit incorporating both TRPV1 activity and solubility was conducted. Substitution of the isoxazole-3-carboxamide with the bespoke 1S, 3R-3-aminocyclohexanol motif afforded the requisite balance of potency and solubility. Compounds 32 and 40 were found to have antihyperalgesic effects in the rat CFA Hg assay and induce a mechanism based hyperthermia. |
| Keywords: | TRPV1 antagonist Antihyperalgesia Isoxazoles Hyperthermia |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |