Synthesis and SAR of p38alpha MAP kinase inhibitors based on heterobicyclic scaffolds.

ABSTRACT

The synthesis and structure-activity relationships (SAR) of p38alpha MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38alpha MAP kinase with good cellular potency toward the inhibition of TNF-alpha production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38alpha is also disclosed.