Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Design and synthesis of conformationally restricted capsaicin analogues based in the 1, 3, 4-thiadiazole heterocycle reveal a novel family of transient receptor potential vanilloid 1 (TRPV1) antagonists.

Authors: Carolyne Lespay Rebolledo, Pamela Sotelo-Hitschfeld, Sebastian Brauchi, Miguel Zárraga Olavarría

Journal, date & volume: Eur J Med Chem, 2013 Aug , 66, 193-203

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23796768

Abstract
4-hydroxy-3-methoxybenzaldehyde was used as starting material to obtain a number of 1, 3, 4-thiadiazole alkylamide derivatives. The pharmacological properties of these conformationally restricted capsaicin analogues were evaluated on HEK-293T cells transiently expressing TRPV1 receptor. By means of a highthroughput calcium imaging assay we find that 1, 3, 4-thiadiazoles (compounds 8-15) act as potent antagonists of the capsaicin receptor, inhibiting both, the capsaicin- and temperature-dependent activation. Docking studies suggested a different binding orientation on the vanilloid binding site when compared with capsaicin analogues, such as 5-iodononivamide. Overall, our studies suggest that 1, 3, 4-thiadiazoles interact with capsaicin's binding region of the receptor, although using a different set of interactions within the vanilloid binding pocket.