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 p38α 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. The synthesis, structure–activity relationship and modeling of a series of 5-substituted- N-aryl pyridazinone based p38α 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.