Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonists.
Bioorganic & medicinal chemistry letters 2005 Dec 1; 15(23):5211-7
Xi N N, Bo Y Y, Doherty E EM, Fotsch C C, Gavva N NR, Han N N, Hungate R RW, Klionsky L L, Liu Q Q, Tamir R R, Xu S S, Treanor J JJ, Norman M MH
Chemistry Research and Discovery, Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA 91320, USA. nxi@amgen.com
A thiazole derivative, 2-(2,6-dichlorobenzyl)-N-(4-isopropylphenyl) thiazole-4-carboxamide (1), was identified as a TRPV1 antagonist. We synthesized various thiazole analogs and evaluated them for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. The IC(50) values of the most potent antagonists were ca. 0.050microM in these assays.

