Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity.

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.

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http://dx.doi.org/10.1016/j.bmcl.2008.10.039DOI Listing
December 2008

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