Discovery of Potent 3,5-Diphenyl-1,2,4-oxadiazole Sphingosine-1-phosphate-1 (S1P1) Receptor Agonists with Exceptional Selectivity against S1P2 and S1P3
Journal of Medicinal Chemistry2005Vol. 48(20), pp. 6169–6173
Citations Over TimeTop 10% of 2005 papers
Zhen Li, Weirong Chen, Jeffrey J. Hale, Christopher L. Lynch, Sander G. Mills, Richard Hajdu, Carol Keohane, Mark Rosenbach, James A. Milligan, Gan-Ju Shei, Gary Chrebet, Stephen A. Parent, James D. Bergstrom, Deborah Card, Michael J. Forrest, Elizabeth J. Quackenbush, L. Alexandra Wickham, Hugo M. Vargas, Rose M. Evans, Hugh Rosen, Suzanne Mandala
Abstract
A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P1) receptor agonists with minimal affinity for the S1P2 and S1P3 receptor subtypes. Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy.
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