(7-Benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acids as S1P1 Functional Antagonists

ACS Med Chem Lett. 2014 Nov 25;5(12):1334-9. doi: 10.1021/ml500422m. eCollection 2014 Dec 11.


S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties.

Keywords: FTY720; Gilenya; S1P1 agonist; Sphingosine-1-phosphate; fingolimod.