2242-77-5Relevant academic research and scientific papers
Synthesis and Anti-Proliferation Activity Evaluation of Novel 2-Chloroquinazoline as Potential EGFR-TK Inhibitors
Jin, Hao,Rao, Guo-Wu,Xu, Xuan-Bo,Zhang, Wen,Zheng, Quan
, (2021)
A novel series of 2-chloroquinazoline derivatives had been synthesized and their anti-proliferation activities against the four EGFR high-expressing cells A549, NCI-H1975, AGS and HepG2 cell lines were evaluated. The preliminary SAR study of the scaffold of new compounds showed that the compounds with a chlorine substituent on R3 had a better anti-proliferation activity than those substituted by hydrogen atom or vinyl group. Among them, 2-chloro-N-[2-chloro-4-(3-chloro-4-fluoroanilino)quinazolin-6-yl]acetamide (10b) had the best activity, and the corresponding IC50 were 3.68, 10.06, 1.73 and 2.04 μM, respectively. And compound 10b had better or equivalent activity against four cell lines than Gefitinib. The activity of the compound 10b on the EGFR enzyme was subsequently tested. The Wound Healing of A549, AGS and HepG2 cells by this compound showed that the compound can inhibit the migration of cancer cells. Finally, the action channel of the compound 10b was supported by western blotting experiments. It provides useful information for the design of EGFR-TK inhibitors.
Discovery of novel quinazolines as potential anti-tubulin agents occupying three zones of colchicine domain
Li, Wenlong,Yin, Ying,Shuai, Wen,Xu, Feijie,Yao, Hong,Liu, Jie,Cheng, Keguang,Xu, Jinyi,Zhu, Zheying,Xu, Shengtao
, p. 380 - 390 (2019)
A series of novel quinazolines as tubulin inhibitors occupying three zones of colchicine domain have been designed and synthesized inspired by the recently disclosed crystal structure of verubulin analogue 6 with tubulin. Among the newly synthesized compounds, 19c showed noteworthy potency against K562, HepG2, KB, HCT-8 and MDB-MB-231 cancer cells. In vitro microtubule polymerization assays identified 19c as a potent tubulin assembly inhibitor, the binding mode of which with tubulin was confirmed by molecular modeling studies to occupy three zones of tubulin domain. Furthermore, 19c disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis and depolarized mitochondria of K562 cells. 19c also reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 19c significantly and dose dependently inhibited tumor growth in H22 liver cancer xenograft mouse model. All these results suggested that 19c deserves further research as a novel and potential anti-tubulin agent for the treatment of cancers.
Discovery of novel potent and selective ligands for 5-HT2A receptor with quinazoline scaffold
Deng, Xinxian,Guo, Lin,Xu, Lili,Zhen, Xuechu,Yu, Kunqian,Zhao, Weili,Fu, Wei
supporting information, p. 3970 - 3974 (2015/08/24)
Abstract A series of compounds with quinazoline scaffold were designed, synthesized and evaluated as novel potent 5-HT2A receptor ligands. N-(4-Chlorophenyl)-2-(piperazin-1-yl)quinazolin-4-amine (5o) has a Ki value of 14.04 ± 0.21 nM, with a selectivity more than 10,000 fold over 5-HT1A receptors (D1 and D2-like receptors). The functional assay showed that this compound is an antagonist to 5-HT2A receptor with an IC50 value of 1.66 μM.
Synthesis of Aromatic Carbonyl Compounds via Thallation-Carbonylation of Arenes
Larock, Richard C.,Fellows, Constance A.
, p. 1900 - 1907 (2007/10/02)
Simple arenes, substituted benzylic and β-phenylethyl alcohols, benzoic acid, phenylacetic acid, benzamide, acetanilide, phenylurea, and benzophenone have been thallated under variety of reaction conditions with thallium(III) trifluoroacetate and subsequently carbonylated with 19percent PdCl2, 2 equiv of LiCl, and MgO in either methanol or tetrahydrofuran under 1 atm of carbon monoxide to give aromatic esters, substituted phthalides and 3,4-dihydroisocoumarins, phthalic and homophthalic anhydride, phthalimide, and the ortho-substituted methyl esters of acetanilide, phenylurea, and benzophenone, respectively.The scope and limitations of this approach to aromatic carbonyl compounds are examined.
