Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: Development of novel azabenzofuran TRPA1 antagonists as in vivo tools.

Authors: Katrina W Copeland, Alessandro A Boezio, Eugene Cheung, Josie Lee, Philip Olivieri, Laurie B Schenkel, Qian Wan, Weiya Wang, Mary C Wells, Beth Youngblood, Narender R Gavva, Sonya G Lehto, Stephanie Geuns-Meyer

Journal, date & volume: Bioorg. Med. Chem. Lett., 2014 Jun 6 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24953819

Abstract
The transient receptor potential ankyrin 1 (TRPA1) channel is activated by noxious stimuli including chemical irritants and endogenous inflammatory mediators. Antagonists of this channel are currently being investigated for use as therapeutic agents for treating pain, airway disorders, and itch. A novel azabenzofuran series was developed that demonstrated in vitro inhibition of allyl isothiocyanate (AITC)-induced (45)Ca(2+) uptake with nanomolar potencies against both human and rat TRPA1. From this series, compound 10 demonstrated in vivo target coverage in an AITC-induced flinching model in rats while providing unbound plasma concentrations up to 16-fold higher than the TRPA1 rat IC50.