3区 · 医学
Article
作者: Lin, Linus S. ; Pang, Jianmei ; Reitman, Marc L. ; Dragovic, Jasminka ; Raustad, Kate ; Lanza, Thomas J. ; Strack, Alison M. ; Chioda, Marc ; Chang, Linda ; Guo, Yan ; Palyha, Oksana ; Liu, Ping ; Metzger, Joseph M. ; Lyons, Kathy ; Kelly, Theresa M. ; Nargund, Ravi P. ; Marsh, Donald J. ; Miller, Randy ; Kan, Yanqing ; Wang, Sheng-Ping ; Madeira, Maria ; Gorski, Judith N. ; Chobanian, Harry R. ; Guan, Xiao-Ming
Extensive structure-activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzodiazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.