title: Design, synthesis, and biological evaluation of phenylamino-substituted 6,11-dihydro-dibenzo[b,e]oxepin-11-ones and dibenzo[a,d]cycloheptan-5-ones: novel p38 MAP kinase inhibitors.
abstract: The pathogenesis of chronic inflammatory diseases is promoted by various pro-inflammatory cytokines. p38 MAP kinase seems to be a valid target as it controls proinflammatory cytokine levels on both transcriptional and translational levels. Starting from benzophenone-type inhibitors, a rigidisation strategy lead to 3-amino-6,11-dihydro-dibenzo[b,e]thiepin-11-one, phenylamino-substituted 6,11-dihydro-dibenzo[b,e]oxepin-11-ones, and dibenzo[a,d]cyclohepten-5-ones. Synthesis, p38 inhibition, and CYP-inhibition of selected compounds are described.
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-Universität, Auf der Morgenstelle 8, 72076 Tübingen, Germany. stefan.laufer@uni-tuebingen.de
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Laufer
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: Ahrens
authors.forename: Solveigh C
authors.initials: SC
authors.lastname: Karcher
authors.forename: Jörg S
authors.initials: JS
authors.lastname: Hering
authors.forename: Raimund
authors.initials: R
authors.lastname: Niess
mesh_terms: D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010082:Oxepins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D010082:Oxepins; D047428:Protein Kinase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D048051:p38 Mitogen-Activated Protein Kinases