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

Autor: Guo J; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States. Electronic address: junqing.guo@bms.com., Watterson SH; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Spergel SH; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Kempson J; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Langevine CM; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Shen DR; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Yarde M; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Cvijic ME; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Banas D; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Liu R; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Suchard SJ; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Gillooly K; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Taylor T; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Rex-Rabe S; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Shuster DJ; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., McIntyre KW; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Cornelius G; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., D'Arienzo C; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Marino A; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Balimane P; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Salter-Cid L; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., McKinnon M; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Barrish JC; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Carter PH; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Pitts WJ; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Xie J; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States., Dyckman AJ; Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, United States.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 May 15; Vol. 26 (10), pp. 2470-2474. Date of Electronic Publication: 2016 Apr 01.
DOI: 10.1016/j.bmcl.2016.03.105
Abstrakt: 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.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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