Discovery of a novel series of potent S1P1 agonists

The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.

Graphical abstractThe discovery of a novel series of S1P1 agonists is described. Several single-digit nanomolar S1P1 agonists were discovered, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.Figure optionsDownload full-size imageDownload as PowerPoint slide