1165930-75-5Relevant academic research and scientific papers
Synthesis, Biological Activity, and Crystal Structure of N,N-Diethyl-2-{[7-methoxy-4-(phenylamino)quinazolin-6-yl]oxy}acetamide Derivatives
Cai, Zhi-qiang,Han, Xiao,Hou, Ling,Li, Shuai,Wu, Li-hua
, p. 2286 - 2291 (2021/12/23)
Abstract: A number of novel 4-aminoquinazoline derivatives has been synthesized by four-step synthesis. Structures of the synthesized compounds have been characterized by IR and 1H NMR spectra, element analysis, and single crystal X-ray diffraction. Biological activity of the products has been tested and most of those are characterized by potential antitumor activity against MKN45 cell line. Two compounds exhibit significant inhibitory activity higher than that of Gefitinib used as the positive control. Preliminary structure-activity relationship is considered.
Design, synthesis and biological evaluation of sulfamoylphenyl-quinazoline derivatives as potential EGFR/CAIX dual inhibitors
Zhang, Bin,Liu, Zhikun,Xia, Shengjin,Liu, Qingqing,Gou, Shaohua
, (2021/03/01)
Multi-target, especially dual-target, drug design has become a popular research field for cancer treatment. Development of small molecule dual-target inhibitors through hybridization strategy can provide highly potent and selective anticancer agents. In this study, three series of quinazoline derivatives bearing a benzene-sulfonamide moiety were designed and synthesized as dual EGFR/CAIX inhibitors. All the synthesized compounds were evaluated against epidermoid carcinoma (A431) and non-small cell lung cancer (A549 and H1975) cell lines, which displayed weak to potent anticancer activity. In particular, compound 8v emerged as the most potent derivative against mutant-type H1975 cells, which exhibited comparable activity to osimertinib. Importantly, 8v exhibited stronger anti-proliferative activity than osimertinib against H1975 cells under hypoxic condition. Kinase inhibition studies indicated that 8v showed excellent inhibitory effect on EGFRT790M enzyme, which was 41 times more effective than gefitinib and almost equal to osimertinib. Mechanism studies revealed that 8v exhibited remarkable CAIX inhibitory effect comparable to acetazolamide and significantly inhibited the expression of p-EGFR as well as its downstream p-AKT and p-ERK in H1975 cells. Notably, 8v was found to inhibit the expression of CAIX and its upstream HIF-1α in H1975 cells under hypoxic condition. Molecular docking was also performed to gain insights into the ligand-binding interactions of 8v inside EGFRWT, EGFRT790M and CAIX binding sites.
Synthesis and evaluation of some novel 6-substituted quinazoline derivatives as antitumor agents
Ding, Hai-guan,Cai, Zhi-qiang,Hou, Ling,Hu, Zhi-quan,Jin, Zheng-sheng,Xu, Di,Cao, Hui,Meng, Miao-miao,Xie, Yu-Hui,Zheng, De-qiang
, p. 186 - 190 (2019/05/01)
Summry: A series of novel 6-substituted quinazoline derivatives were synthesised as epidermal growth factor receptor(EGFR) and Human epidermal growth factor receptor 2 (HER2)inhibitors in our lab. The novel compounds were measured for their dual enzyme inhibition as well as their cytotoxic activity on MCF7 cell line. The results revealed that all the compounds showed inhibition of both enzymes. Compound 5c showed the best inhibitory activity against both enzymes and IC50 of its was 2.6 nM against EGFR kinases and 4.3 nM against HER2 kinases, respectively. Most of the measured compounds showed to antitumor activity on MCF7.
Facile Synthesis of Novel Perfluorocarbon-Modulated 4-Anilinoquinazoline Analogues
Shi, Huiping,Lai, Bonan,Chen, Shizhen,Zhou, Xin,Nie, Jing,Ma, Jun-An
, p. 1693 - 1700 (2017/09/06)
4-Anilinoquinazoline analogues stand out among many kinds of small molecules that inhibit the tyrosine kinase activities of epidermal growth factor receptor (EGFR), thus serving as significant molecular targets for anticancer drug design. Herein, a series of novel perfluorocarbon (PFC) modulated 4-anilinoquinazolines were designed and prepared straightforwardly by nucleophilic substitution reaction of various anilinoquinazolines and PFC-derived methanesulfonate. In the presence of base, the reaction proceeded smoothly to afford a wide range of 4-anilinoquinazolines with different substituents on aniline moiety in good to high yields. Furthermore, the PFC-modified analogues of gefitinib and erlotinib were also obtained in 93% and 90% respectively, which may have potential for developing new inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase and fluorinated contrast agents (CA) for 19F MRI.
Synthesis of several new quinazolin-4-amines containing p-toluenesulfonate moiety
Cai, Zhi-Qiang,Jin, Zheng-Sheng,Zheng, De-Qiang,Hou, Ling,Huang, Guan-Wang,Tian, Jun-Qiang,Wang, Guo-Jiang
, p. 573 - 575 (2016/10/05)
A series of novel quinazolin-4-amine derivatives containing p-toluenesulfonate moiety have been synthesised through the reaction of 4-chloro-7-methoxyquinazolin-6-yl acetate with substituted anilines in toluene solution at 90°C. Further treatment of the synthesised compound with ammonium hydroxide gave the corresponding substituted quinazoline derivatives which were subsequently processed through the sulfonyl reaction into quinazolin-4-amines containing p-toluenesulfonate moiety in DMF. Their structures were established by elemental analysis, IR and 1H NMR spectra.
Synthesis and in vitro antitumor activities of novel 4-anilinoquinazoline derivatives
Chandregowda, Venkateshappa,Kush,Chandrasekara Reddy
experimental part, p. 3046 - 3055 (2009/10/02)
A series of 6, 7-dialkoxy-4-anilinoquinazolines were designed, synthesized by substituting different heterocycles on 6-position and a variety of anilines on 4-position of the quinazoline. These novel quinazoline compounds were screened for their cytotoxic effect on epidermal growth factor receptor overexpressing skin epidermoid carcinoma cell line (A431), by using nonoverexpressing tumor cells as negative control (breast adeno carcinoma cell line MCF-7). 2-Butyl-4-chloro-1-{3-[7-methoxy-4-(3-(trifluoromethyl)phenylamino)quinazolin-6-yloxy]-propyl}-1H-imidazole-5-carboxaldehyde (30) and 2-butyl-4-chloro-1-{3-[4-(3-iodophenyl amino)-7-methoxyquinazolin-6-yloxy]propyl}-1H-imidazole-5-carboxaldehyde (33) were found to be more potent against A431 cell line (IC50 3.5 and 3 μM) and their activities are comparable to gefitinib. Insilico docking experiments with human EGFR Tyrosine kinase domain (PDB id-2gs2) indicated that 33 docks at the same position as that of gefitinib involving Val702, Ala719, Ser696, and Lys721.
