Novel tetrahydro-β-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)

A structure–activity relationship study was conducted on a series of tetrahydro-β-carboline-1-carboxylic acid analogs in order to identify the key functionality responsible for activity against the mitogen-activated protein kinase-activated protein kinase 2 enzyme (MK-2). The compounds were further evaluated for their ability to inhibit TNFα production in U937 cells and in vivo. These compounds represent a novel structural class of compounds capable of inhibiting MK-2 with remarkable selectivity.

Graphical abstractA structure–activity relationship study was conducted on a series of tetrahydro-β-carboline-1-carboxylic acid analogs against MK-2. The compounds were evaluated for their ability to inhibit TNFα production in vitro and in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slide