title: Exploring epidermal growth factor receptor (EGFR) inhibitor features: the role of fused dioxygenated rings on the quinazoline scaffold.
abstract: A number of dioxolane, dioxane, and dioxepine quinazoline derivatives have been synthetized and evaluated as EGFR inhibitors. Their cytotoxic activity has been tested against two cell lines overexpressing and not expressing EGFR. Most derivatives were able to counteract EGF-induced EGFR phosphorylation, and their potency was comparable to the reference compound PD153035. The size of the fused dioxygenated ring was crucial for the biological activity, the dioxane derivatives being the most promising class of this series.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Padova, via Marzolo 5, 35131 Padova, Italy. adriana.chilin@unipd.it
authors.forename: Adriana
authors.initials: A
authors.lastname: Chilin
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Conconi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marzaro
authors.forename: Adriano
authors.initials: A
authors.lastname: Guiotto
authors.forename: Luca
authors.initials: L
authors.lastname: Urbani
authors.forename: Francesca
authors.initials: F
authors.lastname: Tonus
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Parnigotto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010082:Oxepins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004146:Dioxanes; D004148:Dioxolanes; D006575:Heterocyclic Compounds, 3-Ring; D010082:Oxepins; D011799:Quinazolines; D066246:ErbB Receptors