Abstract
A series of 3-arylpropionic acids were synthesized as S1P 1 receptor agonists. Structure–activity relationship studies on the pendant phenyl ring revealed several structural features offering selectivity of S1P 1 binding against S1P 2–5. These highly selective S1P 1 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 S1P 1 agonism is primarily responsible for the immunosuppressive efficacy observed in preclinical animal models.
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