1. Academic Validation
  2. Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1)

Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1)

  • Bioorg Med Chem Lett. 2016 May 15;26(10):2470-2474. doi: 10.1016/j.bmcl.2016.03.105.
Junqing Guo 1 Scott H Watterson 2 Steven H Spergel 2 James Kempson 2 Charles M Langevine 2 Ding Ren Shen 2 Melissa Yarde 2 Mary Ellen Cvijic 2 Dana Banas 2 Richard Liu 2 Suzanne J Suchard 2 Kathleen Gillooly 2 Tracy Taylor 2 Sandra Rex-Rabe 2 David J Shuster 2 Kim W McIntyre 2 Georgia Cornelius 2 Celia D'Arienzo 2 Anthony Marino 2 Praveen Balimane 2 Luisa Salter-Cid 2 Murray McKinnon 2 Joel C Barrish 2 Percy H Carter 2 William J Pitts 2 Jenny Xie 2 Alaric J Dyckman 2
Affiliations

Affiliations

  • 1 Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States. Electronic address: [email protected].
  • 2 Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States.
Abstract

The synthesis and structure-activity relationship (SAR) of a series of pyridyl-isoxazole based agonists of S1P1 are discussed. Compound 5b 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.

Keywords

FTY720; Fingolimod; Isoxazole; S1P(1); Sphingosine-1-phosphate; Sphingosine-1-phosphate 1.

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