Piperidine-based heterocyclic oxalyl amides as potent p38α MAP kinase inhibitors

The design and synthesis of a new class of p38 alpha MAP kinase inhibitors based on 4-fluorobenzylpiperidine heterocyclic oxalyl amides are described. Many of these compounds showed low-nanomolar activities in p38 alpha enzymatic and cell-based cytokine TNF alpha production inhibition assays. The optimal linkers between the piperidine and the oxalyl amide were found to be [6,5] fused ring heterocycles. Substituted indoles and azaindoles were favored structural motifs in the cellular assay. (C) 2009 Elsevier Ltd. All rights reserved.