Bioorg Med Chem Lett 2008 Dec 11;18(23):6142-6. Epub 2008 Oct 11.
Novartis Institutes for BioMedical Research, global Discovery Chemistry, WSJ-88.508, CH-4002 Basel, Switzerland.
Pyrrolo-pyrimidones of the general structure 1 were synthesized and evaluated for their potential as MK2 inhibitors. Potent derivatives were discovered which inhibit MK2 in the nanomolar range and show potent inhibition of cytokine release from LPS-stimulated monocytes. These derivatives were shown to inhibit phosphorylation of hsp27, a downstream target of MK2 and are modestly selective in a panel of 28 kinases.