1236188-83-2Relevant 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.
HETEROCYCLIC COMPOUNDS AS S1P1 AGONISTS FOR THE TREATMENT OF AUTOIMMUNE AND VASCULAR DISEASES
-
, (2012/05/20)
Disclosed are compounds of Formula (I) or stereoisomers, salts, or prodrugs thereof, wherein: W is CH2 or O; Q is Formula (II), Formula (III) or Formula (IV); and R1, R2, R3, R4, n, and G are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
TRICYCLIC HETEROCYCLIC COMPOUNDS
-
, (2011/06/16)
Disclosed are compounds of Formula (I) or stereoisomers or salts thereof, wherein: X1, X2, X3, W, Q1, Q2, and G2 are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
