p38 MAP kinase inhibitors. Part 6: 2-Arylpyridazin-3-ones as templates for inhibitor design

p38 inhibitors based on 3,4-dihydropyrido[4,3-d]pyrimidazin-2-one template were synthesized and their SAR explored. Benchmark compounds 30, 35, and 36 were found to be potent against the enzyme. Crystal structure of p38 in complex with 30 indicated a key π-stacking interaction with the pendant tyrosine residue-35 in the glycine-rich loop.

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