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

Autor: Pan S; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Gray NS; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Gao W; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Mi Y; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Fan Y; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Wang X; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Tuntland T; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Che J; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Lefebvre S; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Chen Y; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Chu A; Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States., Hinterding K; Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland., Gardin A; Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland., End P; Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland., Heining P; Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland., Bruns C; Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland., Cooke NG; Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland., Nuesslein-Hildesheim B; Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
Jazyk: angličtina
Zdroj: ACS medicinal chemistry letters [ACS Med Chem Lett] 2013 Jan 04; Vol. 4 (3), pp. 333-7. Date of Electronic Publication: 2013 Jan 04 (Print Publication: 2013).
DOI: 10.1021/ml300396r
Abstrakt: 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.
Databáze: MEDLINE
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