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.

The title compound, 6-(3-chloropropoxy)-4-(2-fluorophenylamino)-7-methoxyquinazoline, was synthesized by selective nucleophilic attack at C-1 of 1-bromo-3-chloropropane by the potassium salt of 4-(2-fluorophenylamino)-7-methoxyquinazolin-6-ol, which was prepared from 7-methoxy-4-oxo-3,4-dihydroquinazolin-6-yl acetate in three steps. The compound crystallized as an ethyl acetate complex (C20H21ClFN3O3, Mr = 405.85), and X-ray crystallography showed that the crystal belongs to the orthorhombic system, space group Pbca with a = 12.7407(4) Å, b = 14.0058(5) Å, c = 21.7726(7) Å, α = 90°, β = 90° and γ = 90°. The whole molecule is stacked into a three-dimensional structure via weak N–H…N hydrogen bonding between molecules. The compound acts as an effective inhibitor on the proliferation of a lung cancer cell line.

以3-[(3-氨基-4-甲基氨基苯甲酰)吡啶-2-基氨基]丙酸乙酯为起始原料,经环合、水解、酰胺化等反应合成了5个新型的达比加群酯衍生物(5a ～5e),其结构经1 H NMR、IR和HR-MS(ESI)表征.并对5a～ 5e进行了凝血活酶抑制活性(IC50)及生物利用度(F)测试.结果 表明:化合物5c的抗凝血活酶活性(IC50)和生物利用度(F)最好,分别为1.4 +-0.1(nM)和6.9％.

Seven novel 4-substituted anilinoquinazoline derivatives(5a～5g) were synthesized from 6-iodoquinazolin-4-one by chlorination, amination, Suzuki coupling and Wittig-Horner reaction.The structures were characterized by 1H NMR and HR-MS(ESI).The in vitro antitumor activities of 5a～5g against human cancer cells A-549, MCF-7 and A431 were investigated by MTT method.The results indicated that 5a ～5g showed good inhibition activities and 5e showed better inhibition activities (IC50＝0.13～5.26 μmol· L-1) than Lapatinib(IC50＝0.21～15.56 μmol· L-1).

Six novel Dabigatran etexilate derivatives(5a~5f) were designed and synthesized from eth-yl 3-[ 3-amino-4-( methylamino )-N-( pyridin-2-yl ) benzamido ] propanoate by the reaction of cycliza-tion, hydrolysis, amidation, etc.The structures were characterized by 1 H NMR, IR and HR-MS (ESI).The clotting enzyme inhibitory activity(IC50) and activated part clotting time(aPTT) of 5a~5f were investigated.The results showed that 5a exhibited best anticoagulant activities with IC50 of 1.25 ±0.1 nmol· L-1 and aPTT of 77.2 ±1.3 s, better than Dabigatran etexilate.

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.

AbstractThe reaction works with 1,1′‐biphenyl‐2‐carboxylic acids only.

The key intermediate, ethyl 3-[2-{[(4-cyanophenyl) amino] methyl}-1-methyl-N-(pyri-din-2-yl)-1H-benzo[d] imidazole-5-carboxamido]propanoate, in total yield of 79.6%, was synthe-sized by ammoniation reaction of 4-aminobenzonitrile, then amidation with ethyl 3-{[ 3-amino-4-(methylamino) benzoyl]-pyridin-2-ylamino}propanoate and ring-formation.The structure was con-firmed by 1 H NMR and ESI-MS.

A one-pot palladium-catalyzed synthesis of fluoronones via decarboxylative cyclization is reported. This protocol offers good yields and tolerates a broad range of functional groups. Based on the extensive experimental data, we propose a plausible decarboxylative insertion mechanism.