1146395-46-1Relevant articles and documents
Short-acting T-type calcium channel antagonists significantly modify sleep architecture in rodents
Yang, Zhi-Qiang,Schlegel, Kelly-Ann S.,Shu, Youheng,Reger, Thomas S.,Cube, Rowena,Mattern, Christa,Coleman, Paul J.,Small, Jim,Hartman, George D.,Ballard, Jeanine,Tang, Cuyue,Kuo, Yuhsin,Prueksaritanont, Thomayant,Nuss, Cindy E.,Doran, Scott,Fox, Steve V.,Garson, Susan L.,Li, Yuxing,Kraus, Richard L.,Uebele, Victor N.,Taylor, Adekemi B.,Zeng, Wei,Fang, Wei,Chavez-Eng, Cynthia,Troyer, Matthew D.,Luk, Julie Ann,Laethem, Tine,Cook, William O.,Renger, John J.,Barrow, James C.
scheme or table, p. 504 - 509 (2011/03/20)
A novel phenyl acetamide series of short-acting T-type calcium channel antagonists has been identified and evaluated using in vitro and in vivo assays. Heterocycle substitutions of the 4-position of the phenyl acetamides afforded potent and selective antagonists that exhibited desired short plasma half-lives across preclinical species. Lead compound TTA-A8 emerged as a compound with excellent in vivo efficacy as indicated by its significant modulation of rat sleep architecture in an EEG telemetry model, favorable pharmacokinetic properties, and excellent preclinical safety. TTA-A8 recently progressed into human clinical trials, and in line with our predictions, preliminary studies (n = 12) with a 20 mg oral dose afforded a high Cmax of 1.82 ± 0.274 μM with an apparent terminal half-life of 3.0 ± 1.1 h.
