2. Academic Validation
  3. Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator

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

  • ACS Med Chem Lett. 2013 Jan 4;4(3):333-7. doi: 10.1021/ml300396r.
Shifeng Pan 1,  Nathanael S Gray 1,  Wenqi Gao 1,  Yuan Mi 1,  Yi Fan 1,  Xing Wang 1,  Tove Tuntland 1,  Jianwei Che 1,  Sophie Lefebvre 1,  Yu Chen 1,  Alan Chu 1,  Klaus Hinterding 2,  Anne Gardin 2,  Peter End 2,  Peter Heining 2,  Christian Bruns 2,  Nigel G Cooke 2,  Barbara Nuesslein-Hildesheim 2
Affiliations

Affiliations

  • 1 Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
  • 2 Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
PMID: 24900670 DOI: 10.1021/ml300396r
Abstract

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.

Keywords

S1P receptor; S1P1 agonist; lymphocytes.

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