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

Abstract Two series of fused tricyclic indoles were identified as potent and selective S1P 1 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 S1P 3 receptor in vitro, and correspondingly did not produce S1P 3 mediated bradycardia in telemeterized rat.