Discovery of 5-substituted-N-arylpyridazinones as inhibitors of p38 MAP kinase

Kevin D Jerome; Michael E Hepperle; John K Walker; Li Xing; Rajesh V Devraj; Alan G Benson; John E Baldus; Shaun R Selness

doi:10.1016/j.bmcl.2010.03.088

Discovery of 5-substituted-N-arylpyridazinones as inhibitors of p38 MAP kinase

Bioorg Med Chem Lett. 2010 May 15;20(10):3146-9. doi: 10.1016/j.bmcl.2010.03.088. Epub 2010 Mar 31.

Authors

Kevin D Jerome¹, Michael E Hepperle, John K Walker, Li Xing, Rajesh V Devraj, Alan G Benson, John E Baldus, Shaun R Selness

Affiliation

¹ Pfizer Global Research and Development, St. Louis Laboratories, Chesterfield, MO 63017, USA. jerome52@sbcglobal.net

PMID: 20395140
DOI: 10.1016/j.bmcl.2010.03.088

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.

MeSH terms

Anti-Infective Agents / chemical synthesis
Anti-Infective Agents / chemistry*
Anti-Infective Agents / pharmacology
Binding Sites
Computer Simulation
Drug Discovery
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
Mitogen-Activated Protein Kinase 14 / metabolism
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Pyridazines / chemical synthesis
Pyridazines / chemistry*
Pyridazines / pharmacology
Structure-Activity Relationship

Substances

Anti-Infective Agents
Protein Kinase Inhibitors
Pyridazines
Mitogen-Activated Protein Kinase 14