Figure 2.

Design strategies of the four series of inhibitors. Because the parent compounds of series 1 and 2, indole and PF-0684003, respectively, do not interact with the heme iron, various heme binding ligands were attached to the indole scaffold. The imidazole ring interacts with the heme iron, and thus various fragments were attached to the phenyl ring in series 3 and the imidazole ring in series 4 to strengthen the binding to the active site of IDO1.