Discovery of S1P agonists with a dihydronaphthalene scaffold

Structure–activity relationship of sphingosine-1-phosphate receptor agonists was examined. Cinnamyl derivative 1 was modified to improve S1P1 agonistic activity as well as selectivity over S1P3 agonistic activity. Dihydronaphthalene derivative 10d was identified as a potent S1P1 receptor agonist with high selectivity against S1P3 and enhanced efficacy in lowering peripheral lymphocyte counts in mice.

Structure–activity relationship of sphingosine-1-phosphate receptor agonists was examined. Novel S1P agonists with a dihydronaphthalene scaffold were identified.Figure optionsDownload as PowerPoint slide