1236189-33-5Relevant articles and documents
Potent and Selective Agonists of Sphingosine 1-Phosphate 1 (S1P1): Discovery and SAR of a Novel Isoxazole Based Series
Watterson, Scott H.,Guo, Junqing,Spergel, Steve H.,Langevine, Charles M.,Moquin, Robert V.,Shen, Ding Ren,Yarde, Melissa,Cvijic, Mary Ellen,Banas, Dana,Liu, Richard,Suchard, Suzanne J.,Gillooly, Kathleen,Taylor, Tracy,Rex-Rabe, Sandra,Shuster, David J.,McIntyre, Kim W.,Cornelius, Georgia,D'Arienzo, Celia,Marino, Anthony,Balimane, Praveen,Warrack, Bethanne,Salter-Cid, Luisa,McKinnon, Murray,Barrish, Joel C.,Carter, Percy H.,Pitts, William J.,Xie, Jenny,Dyckman, Alaric J.
, p. 2820 - 2840 (2016/04/10)
Sphingosine 1-phosphate (S1P) is the endogenous ligand for the sphingosine 1-phosphate receptors (S1P1-5) and evokes a variety of cellular responses through their stimulation. The interaction of S1P with the S1P receptors plays a fundamental physiological role in a number of processes including vascular development and stabilization, lymphocyte migration, and proliferation. Agonism of S1P1, in particular, has been shown to play a significant role in lymphocyte trafficking from the thymus and secondary lymphoid organs, resulting in immunosuppression. This article will detail the discovery and SAR of a potent and selective series of isoxazole based full agonists of S1P1. Isoxazole 6d demonstrated impressive efficacy when administered orally in a rat model of arthritis and in a mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.
