Design, synthesis and biological evaluation as immunosuppressant of amino alcohol derivatives containing thioether

Abstract

To develop a safer immunosuppressant for organ transplantation and autoimmune disease treatment, in this study, several of novel amino alcohol derivatives containing thioether moiety were synthesized with 7-bromo-tetralin-2-one as starting material, and Suzuki coupling reaction and Bucherer-Bergs reaction as key steps. Their activity as sphingosine 1-phosphate receptor type 1 (S1P1) agonists were evaluated by [γ-35S] GTP binding assay. Among the thioether substituted compounds, compound 10 showed good activity as S1P1 agonist at low micromolar concentration (EC50 = 0.698 μmol/L). The result suggested that it has potential activity against autoimmune diseases and immunosuppressant of organ transplantations.