Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase inhibitors
Christine Dyrager1, Linda Nilsson Möllers, Linda Karlsson Kjäll
1Department of Chemistry, Medicinal Chemistry, University of Gothenburg, SE-41296 Göteborg, Sweden.
Journal of Medicinal Chemistry
|September 13, 2011
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., IC(50) = 17 nm). The inhibitors showed excellent selectivity profiles when tested on a panel of 62 kinases, as well as efficient inhibition of p38 signaling in human breast cancer cells.
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