Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator

A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure–activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzy...

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Published inACS medicinal chemistry letters Vol. 4; no. 3; pp. 333 - 337
Main Authors Pan, Shifeng, Gray, Nathanael S., Gao, Wenqi, Mi, Yuan, Fan, Yi, Wang, Xing, Tuntland, Tove, Che, Jianwei, Lefebvre, Sophie, Chen, Yu, Chu, Alan, Hinterding, Klaus, Gardin, Anne, End, Peter, Heining, Peter, Bruns, Christian, Cooke, Nigel G., Nuesslein-Hildesheim, Barbara
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 14.03.2013
Amer Chemical Soc
Subjects
Chemistry, Medicinal
Letter
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Science & Technology
S1P1 agonist
S1P receptor
lymphocytes
S1P agonist
AGONISTS
SPHINGOSINE-1-PHOSPHATE
INSIGHTS
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Summary:A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure–activity 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–remitting multiple sclerosis.
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ISSN:1948-5875
1948-5875
DOI:10.1021/ml300396r