Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator
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- 作者：Shifeng Pan ; Nathanael S. Gray ; Wenqi Gao ; Yuan Mi ; Yi Fan ; Xing Wang ; Tove Tuntland ; Jianwei Che ; Sophie Lefebvre ; Yu Chen ; Alan Chu ; Klaus Hinterding ; Anne Gardin ; Peter End ; Peter Heining ; Christian Bruns ; Nigel G. Cooke ; Barbara Nuesslein-Hildesheim
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：March 14, 2013
- 年：2013
- 卷：4
- 期：3
- 页码：333-337
- 全文大小：304K
- 年卷期：v.4,no.3(March 14, 2013)
- ISSN：1948-5875
文摘
A novel series of alkoxyimino derivatives as S1P<sub>1sub> agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure鈥揳ctivity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid (32, BAF312, Siponimod), which has recently completed phase 2 clinical trials in patients with relapsing鈥搑emitting multiple sclerosis.