Abstract
Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors of p38MAPK. The most active isomers were those possessing an aryl group alpha and a heteroaryl group beta relative to the nitrogen atom in the 2-position of the central pyridazine. Additionally, substitution in the 6-position of the central pyridazine with a variety of dialkylamino substituents afforded a set of inhibitors having good (p38 IC50 1-20 nM) in vitro activity.
MeSH terms
-
Anti-Inflammatory Agents / chemical synthesis
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / pharmacology
-
Humans
-
Inhibitory Concentration 50
-
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
-
Pyridazines / chemical synthesis
-
Pyridazines / pharmacology*
-
Structure-Activity Relationship
-
p38 Mitogen-Activated Protein Kinases
Substances
-
Anti-Inflammatory Agents
-
Enzyme Inhibitors
-
Pyridazines
-
Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases