Design, Synthesis, and Biological Evaluation of Chromone-Based p38 MAP Kinase Inhibitors

3-(4-Fluorophenyl)-2-(4-pyridyl)chromone derivatives were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38α inhibitors with IC₅₀ in the low nanomolar range (e.g., <b>8a</b>, IC₅₀ = 17 nm). The inhibitors (<b>8a</b> and <b>8e</b>) showed excellent selectivity profiles when tested on a panel of 62 kinases, as well as efficient inhibition (<b>8e</b>) of p38 signaling in human breast cancer cells