Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: Tricyclic 3,4-dihydropyrimidine-2-thione derivatives as potent TRPA1 antagonists.

Authors: Harrie J M Gijsen, Didier Berthelot, Michel A J De Cleyn, Ivo Geuens, Bert Brône, Marc Mercken

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Jan 15 , 22, 797-800

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22222037

Abstract
The transient receptor potential A1 (TRPA1) channel has been implicated in a number of inflammatory and nociceptive processes, and antagonists of the TRPA1 receptor could offer a potential treatment for conditions such as inflammatory or neuropathic pain, airway disorders, and itch. In a high throughput screen aimed at the identification of TRPA1 antagonists, 4-phenyl-2-thioxo-1,2,3,4-tetrahydro-indeno[1,2-d]pyrimidin-5-one (1) was identified as a potent TRPA1 receptor antagonist. A series of analogous tricyclic 3,4-dihydropyrimidine-2-thiones has been prepared via the multi-component Biginelli reaction and subsequent derivatization. This has led to TRPA1 antagonists with potencies around 10nM for both rat and human derived TRPA1 receptors. The activity was shown to reside exclusively in the 4R-enantiomers.