Abstract
The p38 kinases have long been recognized as potentially valuable targets in the development of novel anti-inflammatory therapies. Benzoylpyridinone p38 inhibitors are described that incorporate cell-targeting fragments. The latter groups are appended to the active inhibitor to provide groups that undergo specific esterase cleavage inside the cell, thereby enhancing kinase inhibitory activity. These applications represent the first disclosure of Chroma's synthetic strategy in targeting p38.