title: Design, synthesis and SAR of phenylamino-substituted 5,11-dihydro-dibenzo[a,d]cyclohepten-10-ones and 11H-dibenzo[b,f]oxepin-10-ones as p38 MAP kinase inhibitors.
abstract: The p38 MAP kinase is a key enzyme in inflammatory diseases as it is involved in the biosynthesis of proinflammatory cytokines such as TNF-alpha and IL-1beta. Small molecule p38 inhibitors suppress the production of these cytokines and therefore p38 is a promising drug target for novel anti-inflammatory therapeutics. In this study, we report the design, synthesis, and SAR of novel N-substituted 11H-dibenzo[b,f]oxepin-10-ones and 5,11-dihydro-dibenzo[a,d]cyclohepten-10-ones as p38 inhibitors.
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Dorn
authors.forename: Verena
authors.initials: V
authors.lastname: Schattel
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
mesh_terms: D000893:Anti-Inflammatory Agents; D001665:Binding Sites; D003198:Computer Simulation; D003508:Cycloheptanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D053583:Interleukin-1beta / Q000378:metabolism; D010082:Oxepins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003508:Cycloheptanes; D053583:Interleukin-1beta; D010082:Oxepins; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases