Discovery of 5-substituted-N-arylpyridazinones as inhibitors of p38 MAP kinase.
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.
Jerome
Kevin D
KD
Pfizer Global Research and Development, St. Louis Laboratories, Chesterfield, MO 63017, USA. jerome52@sbcglobal.net
Hepperle
Michael E
ME
Walker
John K
JK
Xing
Li
L
Devraj
Rajesh V
RV
Benson
Alan G
AG
Baldus
John E
JE
Selness
Shaun R
SR
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
D000890:Anti-Infective Agents; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D048308:Mitogen-Activated Protein Kinase 14