title: Design, synthesis and biological evaluation of new classes of thieno[3,2-d]pyrimidinone and thieno[1,2,3]triazine as inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2).
abstract: Driven by a multidisciplinary approach combination (Structure-Based (SB) Three-Dimensional Quantitative Structure-Activity Relationships (3-D QSAR), molecular modeling, organic chemistry and various biological evaluations) here is reported the disclosure of new thienopyrimidines 1-3 as inhibitors of KDR activity and human umbilical vein endothelial cell (HUVEC) proliferation. More specifically, compound 2f represents a new lead compound that inhibits VEGFR-2 and HUVEC at μM concentration. Moreover by the mean of an endothelial cell tube formation in vitro model 2f tartaric acid salt proved to block angiogenesis of HUVEC at μM level.
authors.affiliation: Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, UMR CNRS 7565 SRSMC, Institut Jean Barriol, FR CNRS 2843, Université de Lorraine, 1 Boulevard Arago, 57070 Metz, France.
authors.forename: Enrico
authors.initials: E
authors.lastname: Perspicace
authors.forename: Valérie
authors.initials: V
authors.lastname: Jouan-Hureaux
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.forename: Flavio
authors.initials: F
authors.lastname: Ballante
authors.forename: Stefania
authors.initials: S
authors.lastname: Sartini
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Binbin
authors.initials: B
authors.lastname: Chen
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kirsch
authors.forename: Serge
authors.initials: S
authors.lastname: Schneider
authors.forename: Béatrice
authors.initials: B
authors.lastname: Faivre
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hesse
mesh_terms: D001667:Binding, Competitive; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D011744:Pyrimidinones; D014227:Triazines; D040301:Vascular Endothelial Growth Factor Receptor-2