title: Piperidine-based heterocyclic oxalyl amides as potent p38 alpha MAP kinase inhibitors.
abstract: The design and synthesis of a new class of p38alpha MAP kinase inhibitors based on 4-fluorobenzylpiperidine heterocyclic oxalyl amides are described. Many of these compounds showed low-nanomolar activities in p38alpha enzymatic and cell-based cytokine TNFalpha 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.
authors.affiliation: Department of Medicinal Chemistry and Biology, Scios, Inc, 6500 Paseo Padre Parkway, Fremont, CA 94555, USA.
authors.forename: Babu J
authors.initials: BJ
authors.lastname: Mavunkel
authors.forename: John J
authors.initials: JJ
authors.lastname: Perumattam
authors.forename: Xuefei
authors.initials: X
authors.lastname: Tan
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Luedtke
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Don
authors.initials: D
authors.lastname: Lim
authors.forename: Darin
authors.initials: D
authors.lastname: Kizer
authors.forename: Sundeep
authors.initials: S
authors.lastname: Dugar
authors.forename: Sarvajit
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Yong-jin
authors.initials: YJ
authors.lastname: Xu
authors.forename: Joon
authors.initials: J
authors.lastname: Jung
authors.forename: Albert
authors.initials: A
authors.lastname: Liclican
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Levy
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Tabora
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010070:Oxalates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000577:Amides; D006571:Heterocyclic Compounds; D010070:Oxalates; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C032727:piperidine; D048308:Mitogen-Activated Protein Kinase 14