title: Impact of aryloxy-linked quinazolines: a novel series of selective VEGFR-2 receptor tyrosine kinase inhibitors.
abstract: Three series of 6,7-dimethoxyquinazoline derivatives substituted in the 4-position by aniline, N-methylaniline and aryloxy entities, targeting EGFR and VEGFR-2 tyrosine kinases, were designed and synthesized. Pharmacological activities of these compounds have been evaluated for their enzymatic inhibition of VEGFR-2 and EGFR and for their antiproliferative activities on various cancer cell lines. We have studied the impact of the variation in the 4-position substitution of the quinazoline core. Substitution by aryloxy groups led to new compounds which are selective inhibitors of VEGFR-2 enzyme with IC(50) values in the nanomolar range in vitro.
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UDSL, ICPAL, EA 4481, F-59006 Lille, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Garofalo
authors.forename: Laurence
authors.initials: L
authors.lastname: Goossens
authors.forename: Perrine
authors.initials: P
authors.lastname: Six
authors.forename: Amélie
authors.initials: A
authors.lastname: Lemoine
authors.forename: Séverine
authors.initials: S
authors.lastname: Ravez
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Patrick
authors.initials: P
authors.lastname: Depreux
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008958:Models, Molecular; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D011799:Quinazolines; D020794:Receptor Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2