5-Fluorouracil derivatives. XX. Synthesis and antitumor activity of 5'-O-unsaturated acyl-5-fluorouridines

Various kinds of 5'-O-unsaturated acyl 5-fluorouridines were synthesized to obtain 5-fluorouridine derivatives with low toxicity and high antitumor activity. Antitumor activity of the compounds against L-1210 leukemia in mice was examined, and the 5'-O-4-pentenoyl derivative showed the highest antitumor activity.     

5-Fluorouracil derivatives XXIII. Synthesis and antitumor activities of 1-carbamoyl-5-fluorouracils having aromatic ring

In order to get good antitumor agents especially better than 5-fluorouracil, tegafur and l-hexylcarbamoyl-5-fluorouracil (HCFU), fourty nine 1-carbamoyl-5-fluorouracil having aromatic ring were synthesized from 5-fluorouracil and isocyanates or mines. Antitumor activity was tested in the L1210 tumor system, and 5 compounds gave better value of therapeutic ratio than 5-fluorouracil, tegafur, HCFU. 1-(4-Methoxybenzylcarbamoyl)-5-fluorouracil gave the best result.     

一种水飞蓟宾恶唑衍生物的合成及体外抗肿瘤活性研究

水飞蓟宾多作为保肝药使用,近年来因其在抗肿瘤方面显示的良好潜力而备受关注。为提高水飞蓟宾的抗肿瘤活性,以天然产物水飞蓟宾为先导化合物,合成一系列水飞蓟宾衍生物,其化学结构经1H NMR、13C NMR、MS确证。采用MTT法测试目标化合物对人乳腺癌细胞(MCF-7)和人胃癌细胞(SGC-7901)的体外抗肿瘤活性;并运用分子对接的方法分析目标化合物与HER2靶点的作用方式。结果表明,目标化合物对两种癌细胞的抑制率均优于水飞蓟宾,其中衍生物Ⅱ3和Ⅱ9与阳性对照药拉帕替尼和阿法替尼抑制作用相当,衍生物Ⅱ3和Ⅱ9能与HER2靶蛋白周围的氨基酸残基通过氢键紧密结合。本研究可为新型抗肿瘤药物的研发提供参考。     

5－氟尿嘧啶－卟啉化合物的合成及抗癌活性

以37％－45％的产率合成了六个新的5－氟尿嘧啶-卟啉化合物，通过元素分析 、红外光谱、紫外可见光谱、核磁共振谱和质谱确定了其结构。抗癌试验表明，化 合物A3，A4，A5对Hela（宫颈癌细胞）有明显的抑制作用。     

一种萘酰亚胺衍生物的合成及其体外抗癌活性测定

合成了萘酰亚胺衍生物2-[2-(二甲基氨基)乙基]-6-2-(2-羟乙胺基)乙胺基-1H-苯并异喹啉-1,3(2H)-二酮;利用元素分析、核磁共振谱及质谱分析了其组成和结构;利用MTT法测定了其对人肝癌细胞(HepG2)、人乳腺癌细胞(MDA-MB-231)及人结肠癌细胞(HCT-116)的体外活性.结果表明,标题化合物的体外抗肿瘤活性优于对照品氨萘非特.     

新型二氢卟吩-5-氟尿嘧啶的合成

以系列羟基卟啉为原料,用对甲苯磺酰肼还原,再用四氯对苯醌氧化,制得二氢卟吩(2a~2d);以二环己基碳二亚胺为脱水剂,2与5-氟尿嘧啶-1-基乙酸经酯化反应合成了4个新型二氢卟吩-5-氟尿嘧啶化合物(3a~3d),总收率分别为6.9%, 6.9%, 7.0%和7.6%,其结构经UV-Vis, ¹H NMR, IR和MS表征。     

Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. III. Synthesis and antitumor activity of 3-phenylpiperazinyl-1-trans-propenes

A series of novel 3-[4-phenyl-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes and related compounds were synthesized and evaluated by their cytotoxic activity against several tumor cell lines in vitro and in vivo antitumor activity against some tumor models when administered both intraperitoneally and orally. Compounds with the 3-chloropyridin-2-yl group (9g) and the 3-fluoro-5-substituted phenylpiperazinyl group (29b, c, and e) showed significantly potent cytotoxicity by in vitro testing. Among them, the 3-cyano-5-fluorophenyl derivative (29b) exhibited potent antitumor activity against several tumor cells including human carcinoma without causing undesirable effects in mice.     

The Synthesis of 1-Aryl-5-Fluorouracil

5-Fluorouracil (5-Fu,1)1 is an important antitumor drug. Some derivatives2,3 have shown better therapeutic efficacy than 5-Fu. In order to find much more better antitumor drugs of its derivatives, several attempts have been made and many different types of its derivatives have been prepared at N1, N3 position4~7. Moreover, several different ways have been used for alkylation of 5-Fu7~10. However, up to now, the arylation of 5-Fu at N1 or N3 position hasn't been reported, and the compound o…     

A novel derivative of geldanamycin and its antitumor activity

A new derivative of geldanamycin was synthesized by introducing the 6-cinnamamido-hexyl-amino group into the 17-site of geldanamycin,a heat shock protein 90(Hsp90)inhibitor,to obtain 17-(6-cinnamamido-hexylamino)-17-demethoxygel-danamycin (CNDG).Its in vitro and in vivo anfitumor effects were evaluated by MTT assay and xenografl in nude mice.     

5-氟尿嘧啶-β-环糊精前药的合成

为达到5-氟尿嘧啶结肠靶向释药的目的,合成了不同取代度的5-氟尿嘧啶-β-环糊精前药,其结构经UV-vis,1H NMR,13CNMR,IR,ESI-MS和元素分析表征.     

具有抗癌活性氟尿嘧啶自旋标记衍生物的合成

氟尿嘧啶(5-FU,1)及其一些衍生物(如FT和HCFU等)是临床上广泛使用的抗代谢类抗癌药物,但它们均具有较大的毒副作用.近年来的研究发现,一些稳定的氮氧自由基能迅速穿越细胞膜和血-脑屏障,将其作为载体与某些已知抗癌药物相连接,能显著提高药物对癌细胞的选择性~[1～5],同时也为借助电子自旋共振技术研究药物的作用机理和代谢提供了一种新手段~[4,5].为了寻找新一代高效低毒的抗癌药物和探讨氮氧自由基在标记药物中的作用机制,我们设计合成了一系列1-取代及1,3-二取代的氟尿嘧啶自旋标记衍生物2a～6b.合成路线如下:     

The Synthesis of 6-Alkyl-5-Fluorouracil Derivatives

As an antitumor drug, because of its low efficacy and high toxicity, several modifications have been made on 5-fluorouracil (5-Fu). Some compounds have been found to be highly efficient and much less toxic for the treatment of various solid tumors1~4. Among them, deoxyfluridine (Furtulon) has been used clinically for several years. In our previous work, we have prepared several substituted derivatives of 5-Fu and the primary result shows that some of them have certain antitumor activity5,6. …     

Synthesis and antitumor activity of 5-trifluoromethyl-2,4- dihydropyrazol-3-one nucleosides

2,4-Dihydropyrazole glucosides 3a-3c were prepared and tested for their antitumor activity. The structures of these compounds were established by (1)H and (13)C-NMR spectroscopy. Glucoside 3b shows an in vitro IC(50) value of 16.4 muM against proliferation of the human promyelotic leukemia (HL60) cell line.     

二苯乙烯衍生物的合成及抗肿瘤活性

以甲氧基取代的4’-氨基二苯乙烯与4-溴甲基-5-甲基-1,3-二氧杂环戊烯-2-酮为原料,通过亲核取代反应合成得到了4种新的二苯乙烯衍生物。这些化合物的结构经NMR、IR和元素分析确定。以HeLa、SMMC-7721、BGC-823和A549为受试细胞株,用MTT法测试了这4种化合物的抗肿瘤活性。测试结果表明,这些化合物具有一定的抗肿瘤活性。     

5-氟尿嘧啶修饰卟啉的合成及抗肿瘤活性

合成了一种5-氟尿嘧啶修饰的自由卟啉(5-[2-(5-氟尿嘧啶-3-基)乙氧基苯基]-10,15,20-三(4-甲氧基苯基)卟啉)及其2种金属卟啉配合物:5-[2-(5-氟尿嘧啶-3-基)乙氧基苯基]-10,15,20-三(4-甲氧基苯基)锰卟啉和5-[2-(5-氟尿嘧啶-3-基)乙氧基苯基]-10,15,20-三(4-甲氧基苯基)锌卟啉。 通过紫外可见光谱(UV-Vis)、红外光谱(IR)和核磁共振谱氢谱(¹H NMR)对目标化合物进行了结构表征。 用噻唑蓝法(MTT法)测定了自由卟啉、锰卟啉及锌卟啉分别对肺腺癌细胞株A549、肝癌细胞株Bel7402和人结肠癌细胞株HCT-8的抑制活性。 其中,锰卟啉对人结肠癌细胞株HCT-8的半抑制浓度为IC₅₀为17.8 mg/L,具有一定的细胞毒作用。