Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8

Title: Identification of a novel 2-pyridyl-benzensulfonamide derivative, RQ-00203078, as a selective and orally active TRPM8 antagonist.

Authors: Masashi Ohmi, Yuji Shishido, Tadashi Inoue, Kazuo Ando, Akiyoshi Fujiuchi, Akiko Yamada, Shuzo Watanabe, Kiyoshi Kawamura

Journal, date & volume: Bioorg. Med. Chem. Lett., 2014 Dec 1 , 24, 5364-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25455182

Abstract
A novel series of 2-pyridyl-benzensulfonamide derivatives have been identified as selective and orally active TRPM8 antagonists via high throughput screening (HTS). Exploration of the structure-activity relationships of compound 1 has led to the identification of RQ-00203078 (compound 36) as a highly selective, potent and orally available TRPM8 antagonist. RQ-00203078 demonstrated excellent in vivo activity in a dose dependent manner with an ED50 value of 0.65 mg/kg in the icilin-induced wet-dog shakes model in rats after oral administration and may become an important pharmacological tool for fully assessing the potential therapeutic use of the targets activated by cold stimulation.