Fused tricyclic indoles as S1P₁ agonists with robust efficacy in animal models of autoimmune disease.

Two series of fused tricyclic indoles were identified as potent and selective S1P1 agonists. In vivo these agonists produced a significant reduction in circulating lymphocytes which translated into robust efficacy in several rodent models of autoimmune disease. Importantly, these agonists were devoid of any activity at the S1P3 receptor in vitro, and correspondingly did not produce S1P3 mediated bradycardia in telemeterized rat.