National Center for
3HP2: Crystal Structure of Human p38alpha complexed with a pyridinone compound
Bioorg. Med. Chem. Lett. (2009) 19 p.5851-5856
The identification and evolution of a series of potent and selective p38 inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high-throughput screening hit were prepared and their SAR explored. Their design was guided by ligand bound co-crystals of p38alpha. These efforts resulted in the identification of 12r and 19 as orally active inhibitors of p38 with significant efficacy in both acute and chronic models of inflammation.