Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds

The synthesis and structure–activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.

Graphical abstractThe synthesis and structure–activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.Figure optionsDownload full-size imageDownload as PowerPoint slide