Abstract
The synthesis and in vitro p38 alpha activity of a novel series of benzimidazolone inhibitors is described. The p38 alpha SAR is consistent with a mode of binding wherein the benzimidazolone carbonyl serves as the H-bond acceptor to Met109 of p38 alpha in a manner analogous to the pyridine nitrogen of prototypical pyridylimidazole p38 inhibitors. Potent p38 alpha activity comparable to that of several previously reported p38 inhibitors is observed for this novel chemotype.
MeSH terms
-
Benzimidazoles / chemical synthesis
-
Benzimidazoles / pharmacology*
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / pharmacology*
-
Imidazoles / pharmacology
-
Mitogen-Activated Protein Kinase 14
-
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
-
Mitogen-Activated Protein Kinases / metabolism
-
Molecular Structure
-
Pyridines / pharmacology
-
Structure-Activity Relationship
Substances
-
Benzimidazoles
-
Enzyme Inhibitors
-
Imidazoles
-
L-790070
-
Pyridines
-
Mitogen-Activated Protein Kinase 14
-
Mitogen-Activated Protein Kinases