Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 1 (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead compound. 1 exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 1 should be 1.2–1.4 h. These data indicated that 1 has a short-acting hypnotic property, suggesting that 1 might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 1 and its related compounds should be further evaluated to enable advancement to clinical trials.

Discovery and in vitro and in vivo profiles of N-ethyl-N-[2-[3-(5-fluoro-2-pyridinyl)-1H-pyrazol-1-yl]ethyl]-2-(2H-1,2,3-triazol-2-yl)-benzamide (TASP0428980) as a novel class of dual orexin receptor antagonist

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.