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 S1P1 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.