Pyridazine based inhibitors of p38 MAPK.
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.
McIntyre
Charles J
CJ
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. mcintyre@merck.com
Ponticello
Gerald S
GS
Liverton
Nigel J
NJ
O'Keefe
Stephen J
SJ
O'Neill
Edward A
EA
Pang
Margaret
M
Schwartz
Cheryl D
CD
Claremon
David A
DA
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D011724:Pyridazines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases