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ID: ALA4308862

Journal: Bioorg Med Chem Lett

Title: Discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by the use of docking models.

Authors: Ikegashira K, Ikenogami T, Yamasaki T, Hase Y, Yamaguchi T, Inagaki K, Doi S, Adachi T, Koga Y, Hashimoto H.

Abstract: We report the discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by using a structure-based drug design (SBDD) based on a docking model. The work leads to the representative compound 4a with high CSF-1R inhibitory activity (IC50 = 9.1 nM). The obtained crystal structure of an azetidine compound with CSF-1R, which matched our predicted docking model, demonstrates that the azetidine compounds bind to the DFG-out conformation of the protein as a Type II inhibitor.

CiteXplore: 30442420

DOI: 10.1016/j.bmcl.2018.10.051