title: Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.
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.
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Pan
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Gray
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Gao
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Tove
authors.initials: T
authors.lastname: Tuntland
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Che
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lefebvre
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Genomics Institute of the Novartis Research Foundation , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Chu
authors.affiliation: Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hinterding
authors.affiliation: Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Gardin
authors.affiliation: Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: End
authors.affiliation: Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Heining
authors.affiliation: Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Bruns
authors.affiliation: Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Cooke
authors.affiliation: Novartis Institute for Biomedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nuesslein-Hildesheim
keywords: S1P receptor; S1P1 agonist; lymphocytes