Exploring epidermal growth factor receptor (EGFR) inhibitor features: the role of fused dioxygenated rings on the quinazoline scaffold.
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.
Chilin
Adriana
A
Dipartimento di Scienze Farmaceutiche, Università di Padova, via Marzolo 5, 35131 Padova, Italy. adriana.chilin@unipd.it
Conconi
Maria Teresa
MT
Marzaro
Giovanni
G
Guiotto
Adriano
A
Urbani
Luca
L
Tonus
Francesca
F
Parnigotto
Pierpaolo
P
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
D000970:Antineoplastic Agents; D004146:Dioxanes; D004148:Dioxolanes; D006575:Heterocyclic Compounds, 3-Ring; D010082:Oxepins; D011799:Quinazolines; D066246:ErbB Receptors