Potent 2′-aminoanilide inhibitors of cFMS as potential anti-inflammatory agents

A series of 2′-aminoanilides have been identified which exhibit potent and selective inhibitory activity against the cFMS tyrosine kinase. Initial SAR studies within this series are described which examine aroyl and amino group substitutions, as well as the introduction of hydrophilic substituents on the benzene core. Compound 47 inhibits the isolated enzyme (IC50 = 0.027 μM) and blocks CSF-1-induced proliferation of bone marrow-derived macrophages (IC50 = 0.11 μM) and as such, serves as a lead candidate for further optimization studies.

Graphical abstractA series of 2′-aminoanilides have been identified which exhibit potent and selective inhibitory activity against the cFMS tyrosine kinase. Initial SAR studies within this series are described which examine aroyl and amino group substitutions, as well as the introduction of hydrophilic substituents on the benzene core. Compound 47 inhibits the isolated enzyme (IC50 = 0.027 μM) and blocks CSF-1-induced proliferation of bone marrow-derived macrophages (IC50 = 0.11 μM) and as such, serves as a lead candidate for further optimization studies.Figure optionsDownload full-size imageDownload as PowerPoint slide