Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8

Title: Arylglycine derivatives as potent transient receptor potential melastatin 8 (TRPM8) antagonists.

Authors: Bin Zhu, Mingde Xia, Xiaoqing Xu, Donald W Ludovici, Manomi Tennakoon, Mark A Youngman, Jay M Matthews, Scott L Dax, Raymond W Colburn, Ning Qin, Tasha L Hutchinson, Mary Lou Lubin, Michael R Brandt, Dennis J Stone, Christopher M Flores, Mark J Macielag

Journal, date & volume: Bioorg. Med. Chem. Lett., 2013 Apr 1 , 23, 2234-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23411075

Abstract
A series of arylglycine-based analogs was synthesized and tested for TRPM8 antagonism in a cell-based functional assay. Following structure-activity relationship studies in vitro, a number of compounds were identified as potent TRPM8 antagonists and were subsequently evaluated in an in vivo pharmacodynamic assay of icilin-induced 'wet-dog' shaking in which compound 12 was fully effective. TRPM8 antagonists of the type described here may be useful in treating pain conditions wherein cold hypersensitivity is a dominant feature.