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ID: ALA3351889

Journal: Bioorg Med Chem Lett

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

Authors: Ohmi M, Shishido Y, Inoue T, Ando K, Fujiuchi A, Yamada A, Watanabe S, Kawamura K.

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.

CiteXplore: 25455182

DOI: 10.1016/j.bmcl.2014.10.074