sphingosine-1-phosphate recep. mod. prodrug
for multiple sclerosis, proj. human t1/2 of 5d
from opt. of prior S1P1 modulators
ACS Med. Chem. Lett., Aug. 11, 2020
Bristol-Myers Squibb, Princeton, NJ
“compound 3d” is a prodrug which is phosphorylated in vivo to form a potent sphingosine-1-phopshate receptor modulator. BMS took two previous compounds into the clinic for MS with the goal of differentiating from fingolimod on safety. One potential issue for a previous compound was an overly long (12 day) half-life which could be undesirable in certain settings such as those involving drug-drug interactions. Therefore “compound 3d” was developed to have a shorter preducted human half-life of “only” 5 days.