Author/Authors :
Lin Yan، نويسنده , , Pei Huo، نويسنده , , George Doherty، نويسنده , , Lesile Toth، نويسنده , , Jeffrey J. Hale، نويسنده , , Sander G. Mills، نويسنده , , Richard Hajdu، نويسنده , , Carol A. Keohane، نويسنده , , Mark J. Rosenbach، نويسنده , , James A. Milligan، نويسنده , , Gan-Ju Shei، نويسنده , , Gary Chrebet، نويسنده , , James Bergstrom، نويسنده , , Deborah Card، نويسنده , , Elizabeth Quackenbush، نويسنده , , Alexandra Wickham، نويسنده , , Suzanne M. Mandala، نويسنده ,
Abstract :
A series of 3-arylpropionic acids were synthesized as S1P1 receptor agonists. Structure–activity relationship studies on the pendant phenyl ring revealed several structural features offering selectivity of S1P1 binding against S1P2–5. These highly selective S1P1 agonists induced peripheral blood lymphocyte lowering in mice and one of them was found to be efficacious in a rat skin transplantation model, supporting that S1P1 agonism is primarily responsible for the immunosuppressive efficacy observed in preclinical animal models.
Keywords :
immunosuppression , Lymphocyte lowering , transplantation , 3-Arylpropionic acids , Sphingosine-1-phosphate (S1P) receptors , Agonists
