Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy

Indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as a target for small-molecule immunotherapy for the treatment of a variety of cancers including renal cell carcinoma and metastatic melanoma. This work focuses on the identification of IDO1 inhibitors containing replacements or isosteres for the amide found in BMS-986205, an amide-containing, IDO1-selective inhibitor currently in phase III clinical trials. Detailed subsequently are efforts to identify a structurally differentiated IDO1 inhibitor via the pursuit of a variety of heterocyclic isosteres, leading to the discovery of highly potent, imidazopyridine-containing IDO1 inhibitors.

Automated summary

The focus of this research is on identifying new IDO1 inhibitors for the treatment of renal cell carcinoma and metastatic melanoma. Efforts were made to find structurally differentiated IDO1 inhibitors by pursuing a variety of heterocyclic isosteres, resulting in the discovery of highly potent imidazopyridine-containing IDO1 inhibitors.