- Novel 4-arylaminoquinazolines bearing N,N-diethyl(aminoethyl)amino moiety with antitumour activity as EGFRwt-TK inhibitor
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Herein, four novel 4-arylaminoquinazoline derivatives with N,N-diethyl(aminoethyl)amino moiety were designed, synthesised and evaluated on biological activities in vitro. All synthesised compounds have inhibitory effects against tumour cells (SW480, A549, A431 and NCI-H1975). In particular, 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(5-((N,N-diethyl(aminoethyl))aminomethyl)furan-2-yl)quinazoline (6a) and 6-(5-((N,N-diethylethyl)aminomethyl)furan-2-yl)-4-(4-(E)-(propen-1-yl)phenylamino)quinazoline (6d) were potent antitumour agents which showed high antiproliferative activities against tumour cells in vitro. Moreover, compound 6a could induce late apoptosis of A549 cells at high concentrations and arrest cell cycle of A549 cells in the G0/G1 phase at tested concentrations. Also, compound 6a could inhibit the activity of wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) with IC50 value of 15.60 nM. Molecular docking showed that compound 6a formed three hydrogen bonds with EGFRwt-TK, while lapatinib formed only two hydrogen bonds with the receptor protein. It is believed that this work would be giving a reference for developing anti-cancer drugs targeted EGFR-TK.
- Zhang, Yaling,Chen, Li,Li, Xiabing,Gao, Li,Hao, Yunxia,Li, Baolin,Yan, Yaping
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p. 1668 - 1677
(2019/10/14)
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- Synthesis and in vitro biological evaluation of novel quinazoline derivatives
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A series of novel 4-arylamino-6-(5-substituted furan-2-yl)quinazoline derivatives were designed, synthesized and evaluated on biological activities in vitro. Compound 2a, 3a and 3c exhibited highly anti-proliferation activities on all tested tumor cell lines including SW480, A549, A431 and NCI-H1975 cells. Especially, compound 2a not only exhibited strong anti-proliferation activities against the tumor cell lines which expressed wild type or mutant EGFRL858R/T790M, but also showed the most potent inhibitory activity toward wild type EGFR (IC50?=?5.06?nM). The result of docking with EGFR suggested the binding mode of 2a was similar to that of lapatinib. While Western-blot analyses showed 2a obviously inhibited the activation of EGFR, Akt and Erk1/2 in lung cancer cells at indicated concentration. It is believed that this work would be very useful for developing a new series of TKIs targeting EGFR.
- Zhang, Yaling,Zhang, Ying,Liu, Juan,Chen, Li,Zhao, Lijun,Li, Baolin,Wang, Wei
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p. 1584 - 1587
(2017/03/16)
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- Quinazoline-1-deoxynojirimycin hybrids as high active dual inhibitors of EGFR and α-glucosidase
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A series of novel quinazoline-1-deoxynojirimycin hybrids were designed, synthesized and evaluated for their inhibitory activities against two drug target enzymes, epidermal growth factor receptor (EGFR) tyrosine kinase and α-glucosidase. Some synthesized compounds exhibited significantly inhibitory activities against the tested enzymes. Comparing with reference compounds gefitinib and lapatinib, compounds 7d, 8d, 9b and 9d showed higher inhibitory activities against EGFR (IC50: 1.79–10.71 nM). Meanwhile the inhibitory activities of 7d, 8d and 9c against α-glucosidase (IC50 = 0.14, 0.09 and 0.25 μM, respectively) were obvious higher than that of miglitol (IC50 = 2.43 μM), a clinical using α-glucosidase inhibitor. Interestingly, compound 9d as a dual inhibitor showed high inhibitory activity to EGFRwt tyrosine kinase (IC50 = 1.79 nM), also to α-glucosidase (IC50 = 0.39 μM). The work could be very useful starting point for developing a new series of enzyme inhibitors targeting EGFR and/or α-glucosidase.
- Zhang, Yaling,Gao, Hongliang,Liu, Renjie,Liu, Juan,Chen, Li,Li, Xiabing,Zhao, Lijun,Wang, Wei,Li, Baolin
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p. 4309 - 4313
(2017/09/12)
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- N '-aryl-N, N-dimethyl-formamidine new method for the preparation of (by machine translation)
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The present invention provides a synthetic N '-aryl-N, N-dimethyl-formamidine of the new method. The method firstly to N, N-dimethyl formamide and dimethyl sulfate to imine salt; generating imide salt in the presence of an alkali, and aromatic amine reaction generating N '-aryl-N, N-dimethyl-carboximidamide; the amidines same with other amine function generating [...] compound, can be used in the anti-tumor drug AKT, synthesis of lapatinib and gefitinib, and the like. Mild reaction conditions of the method, is suitable for industrial production. (by machine translation)
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Paragraph 0066-0069
(2017/02/17)
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- A NEW PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to an improved and new process for the preparation of high purity crystalline base of Lapatinib of formula (1) having chemical name N-{3-chloro-4-[(3-fluorobenzyloxy]phenyl}-6-[5-({[2-(methanesulfonyl) ethyl]amino}methyl]-2-furyl]-4-quin -azolinamine and its pharmaceutically acceptable salts.
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- QUINAZOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I) are found to be active in inhibiting replication of flaviviridae viruses, R is C1-C4 alkyl or C1-C4 alkoxy.
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Page/Page column 7
(2008/12/05)
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- TRIAZOLOANILINOPYRIMIDINE DERIVATIVES FOR USE AS ANTIVIRAL AGENTS
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A quinazoline derivative of formula (I), or a pharmaceutically acceptable salt thereof: formula (I) for use in treatment of prevention of a flaviviridae infection.
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Page/Page column 25-26
(2010/11/28)
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- QUINAZOLINE DERIVATIVES AS ANTIVIRAL AGENTS
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Compounds of formula (I) are found to be active in inhibiting replication of flaviviridae Formula (I) wherein: X represents a direct bond or a moiety -L-NR-, wherein R is hydrogen or C1-C4 alkyl, and L represents a C1-Csu
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Page/Page column 14; 15
(2008/06/13)
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