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> - Concepedia

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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>

DOI Full Paper Access

99

Citations

13

References

2005

Year

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,

Journal of Medicinal Chemistry

Drug TargetImmunologyPharmacotherapyS1p3 Receptor AgonismMolecular PharmacologyMedicinal ChemistryExceptional SelectivityMinimal AffinityBiochemistryG Protein-coupled ReceptorReceptor (Biochemistry)Mechanism Of ActionPharmacological AgentPharmacologyPotent 3,5-Diphenyl-1,2,4-oxadiazole Sphingosine-1-phosphate-1Natural SciencesFunctional SelectivityMedicineReceptor AgonistsDrug Discovery

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.

References

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