title: Synthesis and SAR of N-substituted dibenzazepinone derivatives as novel potent and selective alpha(V)beta(3) antagonists.
abstract: Synthesis and SARs of new integrin alpha(V)beta(3) antagonists based on an N-substituted dibenzazepinone scaffold are described. Variation of spacer and guanidine mimetic led to potent compounds exhibiting an IC(50) towards alpha(V)beta(3) in the nanomolar range, high selectivity versus integrin alpha(IIb)beta(3) and efficacy in functional cellular assays.
authors.affiliation: Knoll GmbH, D-67008 Ludwigshafen, Germany. andreas.kling@abbott.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Kling
authors.forename: Gisela
authors.initials: G
authors.lastname: Backfisch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Delzer
authors.forename: Hervé
authors.initials: H
authors.lastname: Geneste
authors.forename: Claudia
authors.initials: C
authors.lastname: Graef
authors.forename: Uta
authors.initials: U
authors.lastname: Holzenkamp
authors.forename: Wilfried
authors.initials: W
authors.lastname: Hornberger
authors.forename: Udo E W
authors.initials: UE
authors.lastname: Lange
authors.forename: Arnulf
authors.initials: A
authors.lastname: Lauterbach
authors.forename: Helmut
authors.initials: H
authors.lastname: Mack
authors.forename: Werner
authors.initials: W
authors.lastname: Seitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Subkowski
mesh_terms: D003984:Dibenzazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019791:Guanidine / Q000737:chemistry; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D003984:Dibenzazepines; D005343:Fibrinolytic Agents; D007202:Indicators and Reagents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D019791:Guanidine