Discovery of BAF312 (Siponimod), a potent and selective S1P receptor modulator

S Pan, NS Gray, W Gao, Y Mi, Y Fan… - ACS medicinal …, 2013 - ACS Publications
S Pan, NS Gray, W Gao, Y Mi, Y Fan, X Wang, T Tuntland, J Che, S Lefebvre, Y Chen, A Chu…
ACS medicinal chemistry letters, 2013ACS Publications
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.
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.
ACS Publications