Departments of Medicinal Chemistry and Biology, Scios, Inc., 6500 Paseo Padre Parkway, Fremont, CA 94555, USA
Abstract:
The design and synthesis of a new class of p38α MAP kinase inhibitors based on 4-fluorobenzylpiperidine heterocyclic oxalyl amides are described. Many of these compounds showed low-nanomolar activities in p38α enzymatic and cell-based cytokine TNFα 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.