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.
- 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.
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.