205259-37-6Relevant articles and documents
Enrichment of novel quinazoline derivatives with high antitumor activity in mitochondria tracked by its self-fluorescence
Zhang, Yaling,Hou, Qiaoli,Li, Xiabing,Zhu, Jiuling,Wang, Wei,Li, Baolin,Zhao, Lijun,Xia, Haibin
, p. 417 - 432 (2019)
In novel synthetic 28 4-arylamino-6-fluoro quinazoline derivatives, compound 3a displayed the most remarkable inhibitory activities against tumor cells (IC50 values ranging between 0.71 and 2.30 μM) in vitro. Importantly, 3a obviously inhibited the proliferation and metastasis of A549 cells in a zebrafish xenograft model, while also mediated cell apoptosis and G0/G1-phase cell cycle arrest in A549 cells. Interestingly, 3a had excellent fluorescence at 439 nm (λex = 375 nm) in DMSO and at 428 nm (λex = 372 nm) in 0.5% DMSO-phosphate buffer, and the self-fluorescent characteristic revealed 3a itself accumulates in the mitochondria of A549 cells, which suggested the antitumor process of 3a may involve the mitochondrial apoptotic pathway. The hypothesis was verified by the increase of the intracellular reactive oxygen species, the decrease of mitochondrial membrane potential, the release of cytochrome C from the mitochondria into the cytoplasm, and the cascade activation of caspase-9 and caspase-3 when A549 cells were treated with 3a. This work has great implications for further development of anticancer agents that can be enriched in mitochondria and can be tracked in real-time in biological systems due to the ideal fluorescence.
Preparation method of erlotinib (by machine translation)
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, (2020/10/21)
2 -4 Difluoro 5 - 2 -dihydroquinazoline -4 ketone and a chlorination reagent are subjected to a condensation reaction in a solvent system; and the obtained 5 - [(6 ethynylphenyl) amino] 7 -3 difluoro quinazoline and diethylene glycol are subjected to an etherification reaction in a base reagent and a solvent system to obtain the erlotinib diecainide obtained by carrying out a cyclization 4 - reaction -4 - in an alkali reagent and a solvent system at a high temperature and carrying 4 - out -6 a 7 - cyclization reaction 3 - in a solvent system at a high temperature and carrying out a cyclization reaction in a 4 - solvent system 3 - at a high temperature.6 7 . The impurity is less and controllable, the next reaction can be directly carried out, the operation is simplified, the good yield can be obtained in each step, the process flow is simplified, and the safety and the environment protection are guaranteed. (by machine translation)
Morpholinylquinazolines
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Paragraph 0203; 0204, (2013/03/26)
The invention relates to compounds of the formulae (I), (II) and (III) in which R1, R2, R3, R4, Y, W1, W2, L, A, Alk, Cyc, Ar, Het1, Het2, Hal and n have the meaning indicated in claim 1, and/or physiologically acceptable salts, tautomers and stereo-isomers thereof, including mixtures thereof in all ratios. The compounds of the formula (I) can be used for the inhibition of serine/threonine protein kinases and for the sensitisation of cancer cells to anticancer agents and/or ionising radiation. The invention also relates to the use of the compounds of the formula (I) in the prophylaxis, therapy or progress control of cancer, tumours, metastases or angiogenesis disorders, in combination with radiotherapy and/or an anticancer agent. The invention furthermore relates to a process for the preparation of the compounds of the formula (I) by reaction of compounds of the formulae (II) and (III) and optionally conversion of a base or acid of the compounds of the formula (I) into one of their salts.
