title: Pyridazine based inhibitors of p38 MAPK.
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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. mcintyre@merck.com
authors.forename: Charles J
authors.initials: CJ
authors.lastname: McIntyre
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Ponticello
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Liverton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Keefe
authors.forename: Edward A
authors.initials: EA
authors.lastname: O'Neill
authors.forename: Margaret
authors.initials: M
authors.lastname: Pang
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Schwartz
authors.forename: David A
authors.initials: DA
authors.lastname: Claremon
mesh_terms: 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
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D011724:Pyridazines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases