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

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.

Graphical abstractPyrrolo-pyrimidones of the general structure 1 were synthesized and evaluated for their potential as MK2 inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide