1373522-74-7Relevant articles and documents
Discovery of novel 1,2,4-thiadiazole derivatives as potent, orally active agonists of sphingosine 1-phosphate receptor subtype 1 (S1P1)
Ren, Feng,Deng, Guanghui,Wang, Hailong,Luan, Linbo,Meng, Qinghua,Xu, Qiongfeng,Xu, Heng,Xu, Xuesong,Zhang, Haibo,Zhao, Baowei,Li, Chengyong,Guo, Taylor B.,Yang, Jiansong,Zhang, Wei,Zhao, Yonggang,Jia, Qiantao,Lu, Hongtao,Xiang, Jia-Ning,Elliott, John D.,Lin, Xichen
supporting information; experimental part, p. 4286 - 4296 (2012/07/03)
A novel series of 1,2,4-thiadiazole compounds was discovered as selective S1P1 agonists. The extensive structure-activity relationship studies for these analogues were reported. Among them, 17g was identified to show high in vitro potency with reasonable free unbound fraction in plasma (Fu > 0.5%), good brain penetration (BBR > 0.5), and desirable pharmacokinetic properties in mouse and rat. Oral administration of 1 mg/kg 17g resulted in significant peripheral lymphocytes reduction at 4 h after dose and rapid lymphocytes recovery at 24 h. 17g showed a transient lymphopenia profile in the repeated dose study in mouse. In addition, 17g also demonstrated efficacy comparable to that of FTY720 (1) in the mouse EAE model of MS.
