1410040-78-6Relevant articles and documents
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 as a novel class of dual orexin receptor antagonist
Suzuki, Ryo,Nozawa, Dai,Futamura, Aya,Nishikawa-Shimono, Rie,Abe, Masahito,Hattori, Nobutaka,Ohta, Hiroshi,Araki, Yuko,Kambe, Daiji,Ohmichi, Mari,Tokura, Seiken,Aoki, Takeshi,Ohtake, Norikazu,Kawamoto, Hiroshi
, p. 1260 - 1275 (2015/03/04)
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 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3 mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2-1.4 h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials.