Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1). Issue 10 (15th May 2016)

• Record Type: Journal Article
• Authors: Guo, Junqing; Watterson, Scott H.; Spergel, Steven H.; Kempson, James; Langevine, Charles M.; 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; Salter-Cid, Luisa; McKinnon, Murray; Barrish, Joel C.; Carter, Percy H.; Pitts, William J.; Xie, Jenny; Dyckman, Alaric J.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 10(2016)
• Page Start: 2470
• Page End: 2474
• Publication Date: 2016-05-15
• Subjects: Sphingosine-1-phosphate -- Sphingosine-1-phosphate 1 -- S1P1 -- Isoxazole -- FTY720 -- Fingolimod; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.105
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The synthesis and structure–activity relationship (SAR) of a series of pyridyl-isoxazole based agonists of S1P1 are discussed. Compound5b provided potent in vitro activity with selectivity, had an acceptable pharmacokinetic profile, and demonstrated efficacy in a dose dependent manner when administered orally in a rodent model of arthritis.