Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Discovery of potent, soluble and orally active TRPV1 antagonists. Structure-activity relationships of a series of isoxazoles.

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

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Aug 1 , 21, 4652-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21723725

Abstract
Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration.