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A novel series of imidazoisoindoles were identified as potent indoleamine-2,3-dioxygenase (IDO) inhibitors. Lead optimization toward improving potency and eliminating CYP inhibition resulted in the discovery of lead compound 25 , a highly potent IDO inhibitor with favorable pharmacokinetic properties. In the MC38 xenograft model in hPD-1 transgenic mice, 25 in combination with the anti-PD-1 monoclonal antibody ( SHR-1210 ) achieved a synergistic antitumor effect superior to each single agent.

Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors