Development of a series of novel 4-anlinoquinazoline derivatives possessing quinazoline skeleton: Design, synthesis, EGFR kinase inhibitory efficacy, and evaluation of anticancer activities in vitro

Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer

“…The effects of the target compounds on proliferation of different cancer cells were determined using MTT assay according to a reported study. 23 Taxol and Erlotinib served as control drugs. Cancer cells used in this assay included K562 (human chronic myelogenous leukemia cells), Jurkat (E6-1) (human T lymphocyte leukemia cells), PANC-1 (human pancreatic carcinoma cells), A549 (human non-small cell lung cancer cells), Colo320 (human colorectal adenocarcinoma cells), Hut78 (human cutaneous lymphoma cells), MDA-MB-435s (human breast ductal carcinoma cells), Hep3B (human hepatoma cells), and PC-3 (human prostate cancer cells); and the concentration of the target compounds (A1-A4 and B1-B13) were 10 μmol/L.…”

“…[17][18][19] Up to now, most approaches have been adopted to enhance the potency and selectivity of these quinazoline derivatives in terms of differing functional groups on the C6 and C7 regions or changing the substituents on the 4-anilino group. [20][21][22][23][24][25][26] However, the exploration of the flexibility limitation of the NH spacer on 4-aminoquinazoline score is rarely reported. In fact, it would be essential to know how the flexibility of the NH spacer affects the TKI's inhibitory activity for further drug design.…”

Molecular Docking Investigation and Pharmacokinetic Properties Prediction of Some Anilinopyrimidines Analogues as Egfr T790m Tyrosine Kinase Inhibitors

“…The crystal structure of EGFR enzyme with pdb entry codes 3IKA covalently binding to WZ4002 was downloaded from the RCSB protein data bank database (https://www.rcsb.org/ ) [23]. In order to identify the amino acid residues in the active site of the enzymes, the enzymes were visualized with discovery studio since they came with co-crystalline ligands.…”

“…The co-crystalized ligand with plant score of −79.7418 was found to interact with the following amino acid residues in the active site of the target MET793, PHE723, LEU718, PHE723, VAL726, LEU718, VAL726, LEU718, and LEU844, respectively (Figure 8). The epidermal growth factor receptor is a well-validated target for lung cancer therapy, many researchers in different literatures had used EGFR as target in lung cancer therapy, to mention but few the work reported by [23,[28][29][30], respectively.…”

N- and / or O- Alkylation of Quinazolinone Derivatives

“…The results show that a different synthesis route must be used to obtain O-alkylation products. It turned out that in order to realize this, quinazolin-4-one derivatives must first be converted to the corresponding 4-chloroquinazolines by the action of thionyl chloride [41] or phosphorus oxychloride [42] followed by a stage of alcoholysis (Scheme 4). The 4-chloro-6,7-dimethoxyquinazoline (12) obtained in this way was subjected to alcoholysis with butanol and benzyl alcohol.…”