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

The design and synthesis of a new class of p38α MAP kinase inhibitors based on 4-fluorobenzylpiperidine heterocyclic oxalyl amidesare described. Many of these compounds showed low-nanomolar activities in p38α enzymatic and cell-based cytokine TNFα production inhibitionassays. The optimal linkers between the piperidineand the oxalyl amidewere found to be [6,5] fused ring heterocycles. Substituted indoles and azaindoles were favored structural motifsin the cellular assay.