Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Structure-activity studies of a novel series of isoxazole-3-carboxamide derivatives as TRPV1 antagonists.

Authors: Ronald Palin, Lynn Abernethy, Nasrin Ansari, Kenneth Cameron, Tom Clarkson, Maureen Dempster, David Dunn, Anna-Marie Easson, Darren Edwards, John Maclean, Katy Everett, Helen Feilden, Koc-Kan Ho, Steve Kultgen, Peter Littlewood, Duncan McArthur, Deborah McGregor, Hazel McLuskey, Irina Neagu, Stuart Neale, Lesley-Anne Nisbet, Michael Ohlmeyer, Quynhchi Pham, Paul Ratcliffe, Yajing Rong, Andrew Roughton, Melanie Sammons, Robert Swanson, Heather Tracey, Glenn Walker

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Feb 1 , 21, 892-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21236666

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.