Design, synthesis and biological evaluation of novel 3,4-dihydro-2H-[1,4]oxazino [2,3-f]quinazolin derivatives as EGFR-TKIs

• Published in: Bioorganic & medicinal chemistry letters 2023-01, Vol.80, p.129104-129104, Article 129104
• Main Authors: Qin, Xuemei, Liu, Peng, Li, Yihai, Hu, Liming, Liao, Yexin, Cao, Tingting, Yang, Lifang
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; EGFR inhibitors; ErbB Receptors; Molecular Structure; NSCLC; Protein Kinase Inhibitors - chemistry; Protein-Tyrosine Kinases; Quinazolin derivatives; Structure-Activity Relationship; Tyrosine kinases
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2022.129104

[Display omitted] Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFRwt kinase (IC50 ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFRwt tyrosine kinase with IC50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC50) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents.