Discovery of a Potent, S1P(3)-Sparing Benzothiazole Agonist of Sphingosine-1-Phosphate Receptor 1 (S1P(1))

[摘要]：Optimization of a benzofuranyl SIP, agonist lead compound (3) led to the discovery of 1-(3-fluoro-4-(5-(2-fluorobenzyl)benzo[d]thiazol-2-yl)benzyl)-azetidine- 3-carboxylic acid (14), a potent SIP, agonist with minimal activity at S1P(3). Dosed orally at 0.3 mg/kg, 14 significantly reduced blood lymphocyte counts 24 h postdose and attenuated a delayed type hypersensitivity (DTH) response to antigen challenge.

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