title: Indole-based heterocyclic inhibitors of p38alpha MAP kinase: designing a conformationally restricted analogue.
abstract: p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in settings of both chronic and acute inflammation has led efforts to find inhibitors of this enzyme as possible therapies for diseases such as rheumatoid arthritis, where p38alpha activation is thought to play a causal role. Herein, we report structure-activity relationship studies on a series of indole-based heterocyclic inhibitors that led to the design and identification of a new class of p38alpha inhibitors.
authors.affiliation: Scios Inc., 820 West Maude Avenue, Sunnyvale, CA 94086, USA.
authors.forename: Babu J
authors.initials: BJ
authors.lastname: Mavunkel
authors.forename: Sarvajit
authors.initials: S
authors.lastname: Chakravarty
authors.forename: John J
authors.initials: JJ
authors.lastname: Perumattam
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Luedtke
authors.forename: Xi
authors.initials: X
authors.lastname: Liang
authors.forename: Don
authors.initials: D
authors.lastname: Lim
authors.forename: Yong-jin
authors.initials: YJ
authors.lastname: Xu
authors.forename: Maureen
authors.initials: M
authors.lastname: Laney
authors.forename: David Y
authors.initials: DY
authors.lastname: Liu
authors.forename: George F
authors.initials: GF
authors.lastname: Schreiner
authors.forename: John A
authors.initials: JA
authors.lastname: Lewicki
authors.forename: Sundeep
authors.initials: S
authors.lastname: Dugar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007211:Indoles; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases