Discovery of Potent 3,5-Diphenyl-1,2,4-oxadiazole Sphingosine-1-phosphate-1 (S1P1) Receptor Agonists with Exceptional Selectivity against S1P2 and S1P3

200599 citationsJournal Articlegreen Open Access

Authors

Zhen Li

Weirong Chen

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.

Topics & Keywords

Sphingolipid Metabolism and Signaling Lipid Membrane Structure and Behavior Endoplasmic Reticulum Stress and Disease

Publication Details

Published in: Journal of Medicinal Chemistry

Volume 48, Issue 20, pp. 6169-6173

DOI: 10.1021/jm0503244

Field-Weighted Citation Impact: 2.95

Command Palette

Discovery of Potent 3,5-Diphenyl-1,2,4-oxadiazole Sphingosine-1-phosphate-1 (S1P<sub>1</sub>) Receptor Agonists with Exceptional Selectivity against S1P<sub>2</sub> and S1P<sub>3</sub>

Authors

Abstract

Topics & Keywords

Publication Details