231278-84-5Relevant articles and documents
Preparation method of 6-substituted furanyl-4-substituted aminoquinazoline derivative and key intermediate thereof
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, (2020/02/14)
The invention relates to a preparation method of a 6-substituted furanyl-4-substituted aminoquinazoline derivative and a key intermediate thereof. 2-halo-5-cyanobenzoate and 3-chloro-4-(3-fluorobenzyloxy)aniline are used as raw materials, and 6-cyano-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline is obtain through an amidation reaction, a formamidine salt substitution reaction and a condensation reaction; then 6-(furan-2-yl)-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline or 6-(5-formylfuran-2-yl)-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline are obtained througha Grignard reaction and an acidification reaction; and then lapatinib or selatinib are prepared through a Mannich reaction or imidization and a reductive amination reaction. The preparation method hasthe advantages that the raw materials are cheap and are easily available, selectivity of the reaction is high, purity of the product is high, and industrial production is facilitated.
Novel 4-arylaminoquinazolines bearing N,N-diethyl(aminoethyl)amino moiety with antitumour activity as EGFRwt-TK inhibitor
Zhang, Yaling,Chen, Li,Li, Xiabing,Gao, Li,Hao, Yunxia,Li, Baolin,Yan, Yaping
, p. 1668 - 1677 (2019/10/14)
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.
Preparation lapatinib method and intermediate
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, (2017/10/06)
The invention provides a compound as shown in formula (X), and the formula is as shown in the specification, and the compound can be used for preparing lapatinib and a medically acceptable intermidate thereof.