Stereochemistry–activity relationship of orally active tetralin S1P agonist prodrugs

Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (−)-(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified as a good SphK2 substrate and potent S1P1 agonist with good oral bioavailability.

Graphical abstractThe synthesis, characterization and stereochemistry activity relationship of tetralin S1P agonist prodrugs is reported. (2R,2′S)-5 (ED50 = 0.1 mg/kg) was identified as a good SphK2 substrate and potent S1P1 agonist with good oral bioavailability.Figure optionsDownload full-size imageDownload as PowerPoint slide