Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase inhibitors

Abstract

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 IC 50 in the low nanomolar range (e.g., 8a, IC 50 = 17 nm). The inhibitors (8a and 8e) showed excellent selectivity profiles when tested on a panel of 62 kinases, as well as efficient inhibition (8e) of p38 signaling in human breast cancer cells. © 2011 American Chemical Society.