Identification of Selective Imidazopyridine CSF1R Inhibitors.

Colony stimulating factor-1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase expressed on members of the mononuclear phagocyte system (MPS), plays a key role in the proper functioning of macrophages, microglia, and related cells. Aberrant signaling through CSF1R has been associated with a variety of disease states, including cancer, inflammation, and neurodegeneration. In this Letter, we detail our efforts to develop novel CSF1R inhibitors. Drawing on previously described compounds, including GW2580 ( 4 ), we have discovered a novel series of compounds based on the imidazo[4,5- b ]pyridine scaffold. Initial structure-activity relationship studies culminated in the identification of 36 , a lead compound with potent CSF1R biochemical and cellular activity, acceptable in vitro ADME properties, and oral exposure in rat.
Competing Interests: The authors declare the following competing financial interest(s): All authors are or were employees of Sanofi and may have stock and/or stock options.
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