title: Discovery of 5-substituted-N-arylpyridazinones as inhibitors of p38 MAP kinase.
abstract: The synthesis, structure-activity relationship and modeling of a series of 5-substituted-N-aryl pyridazinone based p38alpha inhibitors are described. In comparing the series to the similar N-aryl pyridinone series, it was found that the pyridazinones maintained a weaker interaction to the p38 enzyme, and therefore showed generally weaker binding than the pyridinones.
authors.affiliation: Pfizer Global Research and Development, St. Louis Laboratories, Chesterfield, MO 63017, USA. jerome52@sbcglobal.net
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Jerome
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hepperle
authors.forename: John K
authors.initials: JK
authors.lastname: Walker
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Rajesh V
authors.initials: RV
authors.lastname: Devraj
authors.forename: Alan G
authors.initials: AG
authors.lastname: Benson
authors.forename: John E
authors.initials: JE
authors.lastname: Baldus
authors.forename: Shaun R
authors.initials: SR
authors.lastname: Selness
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D055808:Drug Discovery; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D048308:Mitogen-Activated Protein Kinase 14