新型4-氨基喹唑啉衍生物的合成及其抗肿瘤活性

以香草醛为起始原料,与1-溴-3-氯丙烷经烷基化反应后,再与盐酸羟胺反应制得4-(3-氯丙氧基)-3-甲氧基苯腈(3);3经硝酸硝化、铁粉还原后,与N,N-二甲基甲酰胺二甲缩醛反应制得N-[5-(3-氯丙氧基)]-2-腈基-4-甲氧基苯基-N,N-二甲基甲酰胺(6);6与3-氯-4-氟苯胺合环后与芳香醚经取代反应合成了7个新型的4-氨基喹唑啉衍生物(9a~9g),其结构经1H NMR,13C NMR,IR和元素分析表征。初步生物活性测定结果表明:在用药量为10μmol·L-1时,N-(3-氯-4-氟苯基)-7-[3-(2-氯基苯氧基)丙氧基]-6-甲氧基喹唑啉-4-胺(9d)和5-氯-2-【3-{4-[(3-氯-4-氟苯基)胺]-6-甲氧基喹唑啉}-7-氧丙氧基】苯甲醛(9g)对人乳腺癌细胞Bcap-37的抑制率分别为61.4%和78.9%。     

新型氨基喹唑啉化合物的合成及其抗肿瘤活性

以2-氰基-4-硝基苯胺为原料,设计并合成了6个新型的氨基喹唑啉类化合物(5a~5c和6a~6c),其结构经1H NMR,13C NMR和ESI-MS表征。初步的抗肿瘤活性测定结果表明,6-(4-甲酸甲酯苯甲酰胺基)-4-(4-甲基-3-三氟甲基苯胺基)喹唑啉(5b)对人乳腺癌细胞MDA-MB-231和人宫颈癌细胞HELA的抑制活性较好,其IC50分别为4.50μM和3.3μM,优于阳性对照药Gefitinib。     

喹唑啉类衍生物的合成及其抗肿瘤活性

以异香草醛为原料,设计并合成了8个喹唑啉类衍生物(8a～8h),其结构经1H NMR,13C NMR和MS确证。初步抗肿瘤活性测试结果表明,8a～8h对人乳腺癌细胞Bcap-37具有一定程度的体外活性抑制作用。     

新型含三氟甲基喹唑啉衍生物的设计合成及抗肿瘤活性研究

为了从喹唑啉衍生物中寻找高活性的抗肿瘤分子,以2-氨基苯甲酰胺为原料,经过三氟乙酰化、环化、氯代以及偶联反应等,合成了21个2-三氟甲基喹唑啉类化合物,并通过¹H NMR、¹³C NMR、¹⁹F NMR进行结构确证。采用四唑盐（MTT）法评价目标化合物的体外抗肿瘤活性,结果表明,部分所合成的喹唑啉衍生物对人前列腺癌细胞（PC3、LNCaP）、人慢性髓系白血病细胞（K562）、宫颈癌细胞（Hela）以及人肺癌细胞（A549）具有抗增殖活性,其中活性较好的化合物5a和5b在5μmol/L时对LNCaP细胞增殖的抑制活性分别为61.7%、62.8%。此外N-甲基化产物5a和5b的体外抗肿瘤活性较原型化合物（4a和4b）显著提高,这为该类化合物的深入研究提供了参考依据。     

4-氨基喹唑啉类衍生物的合成及体外抗肿瘤活性

2-氨基-4,5-二甲氧基苯甲酸为起始原料,经环化、氯化和取代反应,合成了5个4-氨基喹唑啉类化合物3a~3e,其结构经¹H NMR和MS测试技术进行了表征。采用MTT法测试了化合物3a~3e对人乳腺癌细胞（MCF-7）、人肺癌细胞（A549）和人前列腺癌细胞（PC-3）的体外抗肿瘤活性。结果表明：3b、3d和3e对3种细胞株的活性有一定的抑制作用,并且对A549表现出了一定程度的选择性。通过分子对接模拟研究AMD和3b与 DNA序列d(CGATCG) 之间的相互作用。      

基于HER_2受体的新型喹唑啉衍生物的合成及其抗肿瘤活性

以取代4-[(4-硝基苯氧基)亚甲基]哌啶为原料,经还原、取代、suzuki和加成4步反应合成了6个新型的喹唑啉衍生物(5a~5f),其结构经1H NMR和ESI-MS表征。用MTT法考察了5a~5f对人脐静脉内皮细胞(HUVEC),人肺癌细胞(A-549),乳腺癌细胞(MCF-7)和人早幼粒白血病细胞(HL-60)的体外活性抑制活性。结果表明:环丙基【4-【【4-【【6-【5-{[(2-甲磺酰基乙基)氨基]甲基}呋喃-2-基】喹唑啉-4-基】氨基】苯氧基】甲基】哌啶-1-基】甲基酮(5b)抑制活性最好,其IC50分别为0.55μg·m L-1,0.18μg·m L-1,0.27μg·m L-1和5.24μg·m L-1,优于阳性对照药拉帕替尼。     

含苯并噻唑的4-氨基喹唑啉衍生物的合成及抗肿瘤活性研究（英文）

为了寻找高效低毒的抗肿瘤药物,设计并合成了一系列新型的含苯并噻唑结构的4-氨基喹唑啉类衍生物,并采用噻唑蓝(MTT)法测定了目标化合物对人乳腺癌细胞系(MCF-7)、人胃癌细胞系(MGC-803)、人前列腺癌细胞系(PC-3)和人高度分化的胃癌细胞系(HGC-27)四种肿瘤细胞的抗增殖活性.结果显示大部分化合物具有较好的抗肿瘤活性,其中2-((苯并[d]噻唑-2-基甲基)硫亚基)-N-(3-氯-4-氟苯基)-喹唑啉-4-胺(13n)对MCF-7、MGC-803、PC-3和HGC-27四种细胞显示出最好的抗增殖活性, IC₅₀值分别为(6.01±0.54),(7.63±0.48),(6.16±0.34)和(7.59±0.62)μmol·L^-1,其活性均优于阳性对照物吉非替尼.分子对接结果显示化合物13n能与表皮生长因子受体(EGFR)很好地结合,为抗肿瘤药物的研究提供了线索.     

新型二唑类4-氨基喹唑啉衍生物的合成及其抗肿瘤活性

N-(3-氯-4-氟苯胺基)-7-(3-氯丙氧基)-6-甲氧基喹唑啉-4-胺与一系列取代二唑类化合物经取代反应合成了6个新型的二唑类4-氨基喹唑啉衍生物(3a~3f),其结构经1H NMR,13C NMR,IR及元素分析表征。用MTT法初步测定了3a~3f对前列腺癌细胞(PC-3)和人乳癌细胞(Bcap-37)的抑制率。结果表明:N-(3-氯-4-氟苯基)-6-甲氧基-7-{3-[5-(4-硝基苯基)-1,3,4-噻二唑-2-巯基]丙氧基}喹唑啉-4-胺和N-(3-氯-4-氟苯基)-7-{3-[5-(4-氯苯基)-1,3,4-噁二唑-2-巯基]丙氧基}-6-甲氧基喹唑啉-4-胺在用药量为10μmol·L-1时对PC-3的抑制率分别为66.8%和72.2%。     

新型4-取代苯胺喹唑啉衍生物的合成与抗肿瘤活性研究

以6-碘喹唑啉-4-酮为原料,经氯代、胺化、Suzuki偶联、Wittig-horner等反应合成了7个新型的4 取代苯胺喹唑啉衍生物(5a~5g),其结构经¹H NMR和HR-MS(ESI)表征。采用MTT法研究了5a~5g对人乳腺癌细胞(MCF-7)、人肺癌细胞(A549)和人皮肤鳞癌细胞（A431）的抑制活性。结果表明：5a~5g对肿瘤细胞均具有明显的抑制活性;其中5e的抑制活性(IC₅₀=0.13~5.26 μmol·L^-1)优于拉帕替尼(IC₅₀=0.21~15.56 μmol·L^-1)。     

6-取代喹唑啉衍生物的合成及抗肿瘤活性研究进展

喹唑啉及其衍生物作为重要的药效团,具有广谱的抗肿瘤生物活性,一直是药物化学研究的热点。本文围绕近年来6-酰胺类、卤代类、醚类、与7-位成环类、杂环类等喹唑啉衍生物的合成及其抗肿瘤活性作用机制研究进行概述,以期为活性更高、毒性更小的新型抗肿瘤化合物的设计合成提供参考。     

Synthesis of Novel Quinazoline Derivatives as Antimicrobial Agents

Quinazoline isothiocyanate 1 reacts with various nucleophiles(nitrogen nucleophiles,oxygen nucleophiles and sulphur nucleophiles)to afford heterocyclic systemes 2-13,Also,the [4 2] cycloaddition reaction of 1 with phenyl isocyanate,benzylidene aryl amine and cinnamic acid derivatives gave novel heterocyclic compounds 14-16,Moreover,the reaction of 1 with active methylene compounds under Michael reaction conditions also was investigated to yield 17 and 18 and it was found that all these reactions proceede via isothiocyanate heterocyclization to furnish non-condensed heterocyclic compoundes,Some of the newly synthesized compounds were tested for their antimicrobial activities.     

Discovery of Novel Quinazoline Derivatives as Potent Antitumor Agents

In this work, we designed and synthesized a novel series of quinazoline derivatives 6–19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound 18 exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC₅₀ value of 0.85 μM, indicating approximately a 32-fold selectivity against GES-1 (IC₅₀ = 26.75 μM). Further preclinical evaluation showed that compound 18 remarkably inhibited the migration of MGC-803 cells, induced cell cycle arrest at G2/M, and induced MGC-803 apoptosis, resulting in decreasing the expression of both Bcl-2 and Mcl-1, and up-regulating the expression of both Bax and cleaved PARP. No death or obvious pathological damage was observed in mice by acute toxicity assay. The in vivo antitumor evaluation suggested that compound 18 significantly decreased the average tumor volume and tumor weight without any effect on body weight, which is better than 5-Fu. Therefore, compound 18 can be used as a lead compound for the further development of antitumor drugs in the future.     

Design,Synthesis of Novel Thiourea and Pyrimidine Derivatives as Potential Antitumor Agents

1,3‐Bis‐(arylidene)thiourea derivatives ( 11a‐c ) were prepared by reacting thiourea ( 9 ) with bezaldehyde, p‐chlorobenzaldehyde or p‐anisaldehyde ( 10a‐c ) respectively. Further reaction of ( 11b ) with acetyl acetone, ethyl acetoacetate, malononitrile and acetic anhydride gave tetrahydropyrimidine‐2‐thiones ( 12‐14 ) and 1,3‐diacetyl thiourea ( 15 ). Compound ( 11b ) reacted with chloroacetyl chloride to give the corresponding pyrimidin‐4‐one derivative ( 16 ). Reaction of ( 12‐14 ) with acetic acid in aqueous sodium nitrite yielded the corresponding oxime derivatives ( 17‐19 ). The triazole ( 20 ) was achieved via refluxing of ( 19 ) in dimethylformamide. Reaction of ( 16 ) with mercaptoacetyl chloride gave the sulfanyl‐acetic acid ( 21 ) which afforded the dihydrazinyl ( 22 ) up on treatment with hydrazine hydrate. Newly synthesized compounds ware characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR and mass spectra). The investigated compounds were screened for their cytotoxicity, i.e. compounds 19 , 20 and 22 exhibited highly potential antitumor activity.     

Synthesis of 4‐Heteroaryl–Quinazoline Derivatives as Potential Anti‐breast Cancer Agents

4‐Heteroaryl or heteroalkyl–quinazoline derivatives were prepared as dual epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor‐2 (VEGFR‐2) inhibitors. The new compounds were tested for their dual enzyme inhibition as well as their cytotoxic activity on MCF7 cell line. The results indicated that almost all the compounds showed moderate dual inhibition of both enzymes. Compound 3 (methyl piperidine‐4‐carboxylate derivative) showed the highest inhibitory activity against both enzymes with IC₅₀ 97.6 and 64.0 µM against EGFR and VEGFR‐2 kinases, respectively. Most of the test compounds showed potent to moderate antitumor activity on MCF7 cell line. Five compounds ( 3 , 9c , 11 , 13 , and 15b ) showed potent cytotoxic activity with IC₅₀ values between 10 and 17 µM .     

新型喹唑啉类酪氨酸激酶化学抑制剂的设计与合成

以6-氨基藜芦酸和醋酸甲脒为起始原料,合成了一系列4-位具有不同芳胺基团,6,7-位引入不同取代基的新型喹唑啉类酪氨酸激酶化学抑制剂,其结构经1H NMR表征.     

Novel Quinazoline Derivatives Bearing a Sulfapyridine Moiety as Anticancer and Radiosensitizing Agents

Quinazoline derivatives posses many types of biological activities and have recently been reported to show substantial antitumor activity in vitro and/or in vivo. There is a variety of mechanisms for their anticancer activity. The present work reports the possible utility of methyl anthranilate in the synthesis of some new quinazoline derivatives, bearing a substituted sulfonamide moiety. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human liver cancer cell line, using doxorubicin as a reference drug. In addition, the most active compounds 14 and 15 were selected and evaluated for their ability to enhance the cell killing effect of γ‐radiation.     

Design,Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents

A series of novel 4-phenoxyquinoline derivatives containing 3-amino-2-cyano-acrylamide framework was designed and synthesized, and the in vitro cytotoxic activities of them against five cancer cell lines(HT-29, H460, A549, MKN-45, and U87MG) were evaluated. Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines as compared with Foretinib. The studies of their preliminary structure-activity relationships(SARs) indicate that the compounds containing methyl groups, especially methyl groups at 4-position of the phenyl ring(moiety B) are more effective. Among them, compound 36 shows the most potent antitumor activities with IC₅₀ values of 0.04, 0.09, 0.67, 0.39 and 1.10 μmol/L against HT-29, H460, A549, MKN-45 and U87MG cell lines, respectively.     

Design,Synthesis and Anticancer Activity Evaluation of Novel Quinazoline Derivatives as EFGR Inhibitors

Malignant tumor is one of the major diseases that seriously threaten human health today. Compared with traditional chemotherapy, targeted drug therapy has become a new idea of tumor therapy. And EGFR(epidermal growth factor receptor) is highly expressed in many human tumor cell lines, which is a biomarker of tumor proliferation. In this paper, small molecule tyrosine kinase inhibitors with quinazoline structure aiming at EGFR were studied. A series of novel quinazoline derivatives(4 a～4 l) have been designed and synthesized from 4-hydroxyquinazoline as the parent core. Structures of target compounds were characterized by ~1H NMR and ~(13)C NMR spectra. The in vitro anticancer activity of compounds 4 a～4 l was evaluated by MTT assay against Hela,MCF-7 and A549 tumor cell lines, and apoptosis-inducing capacity was investigated by Annexin-V/PI staining assay.The results showed that all compounds had good antitumor activity against the test tumor cell lines. Especially,compound 4 a exhibited the best anticancer activity(IC_(50) = 10.23 μM) against Hela cell lines, remarkable ability to induce apoptosis, and low toxicity, which identified 4 a as a promising anticancer drug aiming at EFGR.     

Design,Synthesis, and Biological Evaluation of 1,2,4-Oxadiazole-Isoxazole Linked Quinazoline Derivatives as Anticancer Agents

Russian Journal of General Chemistry - A series of novel 1,2,4-oxadiazole-isoxazole linked quinazoline compounds is designed, synthesized and screened for anticancer activity on four human cancer...