2,5-Disubstituted pyrrolidine carboxylates as potent, orally active sphingosine-1-phosphate (S1P) receptor agonists

A series of 2,5-cis-disubstituted pyrrolidines were synthesized and evaluated as S1P receptor agonists. Compounds 15–21 were identified with good selectivity over S1P3 which lowered circulating lymphocytes after oral administration in mice.

A series of 2-aryl(pyrrolidine-5-yl)acetic acids (e.g., 21) were synthesized and evaluated as S1P receptor agonists. Compounds 15–21 were identified with good selectivity over S1P3 and found to lower peripheral lymphocytes after oral administration in mice.Figure optionsDownload as PowerPoint slide