Synthesis of Some New Pyrimidothienopyridazines and Related Heterocycles

5‐Amino‐3,4‐diphenylthieno[2,3‐c]pyridazine‐6‐carbonitrile 2a was reacted with propylene diamine to give tetrahydropyrimidinyl derivative 3 . The latter compound ( 3 ) underwent certain cyclocondensation reactions to produce pyrimidothienopyridazines 4–6 . Also, the reactions of 5‐amino‐3,4‐diphenylthieno[2,3‐c]pyridazine‐6‐carboxamide with heterocyclic aldehydes and/or cycloalkanones were carried out and their products were identified. Moreover, some novel pyridazinothienopyrimidobenzimidazoles 14–17 were synthesized.     

Synthesis and Antitumor Activity of Tanshinone Analogues

8, 8-Dimethyl-5, 6, 7,8-tetrahydrophenanthrene-3, 4-dione (3) and 8, 8-dimethyl-2- ( 1-hydroxy ethyl) -5,6, 7, 8-tetrahydrophenanthrene-3,4-dione (4), two analogues of the antitumor active tanshinone, were synthesized from anisole. The synthesized compounds 3 and 4 were shown to be highly active against leukemia P-388 cell fine as assayed by in vitro MTT method.     

Synthesis and Antitumor Activity of Capecitabine Derivatives

A series of capecitabine derivatives with a Boc group at the N⁴-position was synthesized and their in vitro antitumor activities against HepG2(liver hepatocellular carcinoma) were primarily evaluated. Some compounds were chosen for further evaluation of their in vivo efficacy on nude mice xenografted human hepatoma HepG2. The results showed that compounds 3 and 6 had considerable in vivo activity against HepG2, with tumor growth inhibition rates of 70% and 64% on day 21, respectively, and 56% and 55% on day 35, respectively, which are roughly comparable to capecitabine(74% and 59% on days 21 and 35, respectively).     

吲哚马来酰亚胺类化合物的合成及其抗肿瘤活性

为寻找具有抗肿瘤活性的新化合物, 设计合成吲哚马来酰亚胺类化合物, 并评价其体外抗肿瘤活性. 以吲哚与2-氯乙酰胺为起始原料, 经取代、缩合等反应合成了单吲哚马来酰亚胺衍生物5a～5t, 以5-硝基吲哚和不同的N-(3-氯丙基)叔胺经取代、还原、缩合等反应得到了双吲哚马来酰亚胺衍生物9a～9f. 共合成了26个未见文献报道的新化合物, 其结构经质谱、元素分析和核磁共振氢谱确证. 采用MTT法, 测试了目标化合物对肿瘤细胞株HL60, ECA-109, A549, SMMC-7721和PC-3的增殖抑制活性, 结果表明部分化合物对所测肿瘤细胞株均显示一定的抑制作用.     

A Simple Synthesis of C-Glucosides Related to the Antitumor Agent Etoposide

Abstract

The synthesis of four new lignan derivatives 2a, 2b, 3a and 3b related to the anticancer agent etoposide has been accomplished. In these compounds a methylene or ethylene group of a C-glucoside separates the glucosidic moiety as present in etoposide (1) from its lignan aglycone bonded by an ethereal function. The key step in the synthesis involves the reaction of a benzylated alditol 4 or 5 and the unprotected 4′-demethylepipodophyllotoxin (6).     

肟醚噻二唑硫醚化合物的合成及其抗肿瘤活性

将2-巯基-5-取代基-1,3,4-噻二唑经与β-氯苯丙酮取代、盐酸羟胺肟化和氯甲基噁二唑醚化,合成了6种3-(5-取代基-1,3,4-噻二唑-2-硫代基)-1-苯基丙酮-O-(5-苯基-1,3,4-噁二唑-2-甲基)肟醚化合物(4a~4f),用1H NMR、IR、MS和元素分析表征了其结构。 用MTT法测试了6种目标化合物对人黑色素瘤细胞株B16、人白血病细胞株HL60和人肝癌细胞株SMMC-7721的体外细胞毒活性。 测试结果表明,部分化合物对3种癌细胞具有潜在的体外生长抑制活性。     

甘草次酸衍生物的合成及其抗癌活性

设计合成了6种甘草次酸衍生物,用元素分析、波谱分析鉴定了它们的结构,并比较了它们的体内、体外抗癌活性,均表现出较好的活性,尤其是化合物Ⅰa,Ⅰb口服效果比盐酸氮芥还好,表现出甘草次酸对氮芥有明显的增效应用。     

N-(5-芳苄叉基饶丹宁)左氧氟沙星酰胺的合成及抗肿瘤活性

为进一步发现氟喹诺酮药物向抗肿瘤活性转化的结构修饰新策略,用酰氨基为左氧氟沙星(1)C-3羧基的电子等排体,5-芳苄叉基饶丹宁为其功能修饰基,设计合成了N-(5-芳苄叉基饶丹宁)左氧氟沙星酰胺类目标化合物(6a-6n)。 体外抗肿瘤活性结果表明,所合成的14个化合物的活性均强于母体左氧氟沙星,且对正常细胞表现出较低的细胞毒性作用。 构效关系表明,增大芳基取代基的体积或供电性均导致抗肿瘤活性的明显降低,反之,吸电子取代苯基或芳香杂环类目标化合物的抗肿瘤活性强于其他取代基类。 其中,硝基化合物6l、呋喃6m和吡啶6n对人胰腺癌细胞株(Capan-1)的半数抑制浓度(IC₅₀) 与对照抗肿瘤药阿霉素(1.6 μmol/L)相当,分别为1.8、0.8和1.3 μmol/L。 因此,芳苄叉基饶丹宁修饰的酰氨基替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。     

拉帕替尼类似物的合成及抗肿瘤活性研究

以N'-(2-氰基-4-碘苯基)-N,N-二甲基甲脒为原料,经过Dimroth重排反应、Suzuki偶联、还原氨化3步反应合成了4种新型的拉帕替尼类似物。借助NMR、IR和HRMS对反应中间体和目标化合物进行结构表征,并采用MTT法在SW480、A549和A431人肿瘤细胞上进行了这些化合物抗肿瘤活性的初步体外评价。结果表明,以上4种化合物均具有明显的抑制肿瘤细胞生长作用,特别是化合物5a对所试肿瘤细胞均表现出良好的生长抑制活性(IC50:5.78~13.38μmol/L),与临床使用的抗肿瘤药物拉帕替尼的活性(IC50:4.80~14.90μmol/L)相当。     

Schiff碱,咪唑金属配合物的合成与抗癌活性

报道一类新的Ｓｃｈｉｆｆ碱和咪唑的混合型金属配合物，即水杨醛缩甘氨酸，咪唑金属配合物和２，４－二羟基苯甲醛缩丙氨酸，咪唑金属配合物的合成，用溴化乙锭荧光分析法研究了这类配合物与ＤＮＡ的相互作用，其中镍配合物与ＤＮＡ的作用明显。     

Synthesis and Biological Activity Test of Some New Five Membered Heterocycles

A new series of 1,3,4‐oxadiazoles, 1,2,4‐triazoles, 1,3,4‐thiadiazoles were synthesized using alkylhydrazides as the starting materials, and then 1,2,4‐triazoles were used to synthesize [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles. All the compounds were evaluated for in vitro antibacterial activity and antitumor activity.     

Synthesis and Antitumor Activity of an Analog of Phthalascidin

Ecteinascidin 743 (Et-743) is an exceedingly potent antitumor agent isolated from the extracts of the marine tunicate Ecteinascidia turbinate1 that is currently undergoing phase Ⅱ/Ⅲ clinical trials in Europe and the United States2. As the result of its …     

萘酰亚胺多胺衍生物的合成及其抗肿瘤活性

设计合成了萘酰亚胺的4种新的多胺衍生物并进行了体外抗肿瘤活性测试。结果表明,这些萘酰亚胺衍生物能够嵌入DNA碱基对中,并且比氨萘非特对肿瘤细胞具有更高的毒性和更好的选择性,其中化合物3b对4种肿瘤细胞的抑制IC50值分别为7.80、5.08、9.78和9.27μmol/L;高内涵活细胞成像系统结果显示,这些化合物可能是通过线粒体通路而导致的细胞凋亡。     

芳香异羟肟酸二烃基锡配合物的合成、表征及其抗癌活性的研究

合成了９个Ｒ_２ＳｎＬ_２型（Ｒ＝乙基、正丁基和苯基；ＨＬ＝苯甲酰异羟肟酸，对羟基苯甲酰异羟肟酸和水杨酰异羟肟酸）和６个［Ｒ_２ＳｎＬ］_２Ｏ型（Ｒ＝乙基、正丁基；ＨＬ同上）二烃基锡新配合物。测定了它们的分子量、红外光谱和核磁共振谱，着重研究了这些配合物的体外抗癌活性。结果表明，这二类配合物对人白血病ＨＬ－６０，艾氏腹水和Ｓ－１８０癌细胞有很好的抑制能力。初步探讨了结构－抗癌活性间的关系。     

阿糖胞苷金属卟啉衍生物的合成及光动力抗肿瘤活性

设计并合成了阿糖胞苷卟啉衍生物(AHP), 并通过金属插入反应获得了4种金属卟啉衍生物, 采用核磁共振、红外光谱、紫外-可见光谱和质谱等手段对化合物的结构进行了表征.光动力抗肿瘤活性实验结果表明, 含药浓度为25 μmol/L的ZnAHP经光照30 min后对人乳腺癌MCF-7细胞的光动力杀伤率平均达(45.86±8.20)%.     

Design,Synthesis and Antitumor Activity of Pyrrolopyrazinone-chalcone Hybrids

A series of pyrrolopyrazinone-chalcone hybrids（12a-12q） was designed,synthesized and screened for their antitumor activity against SKOV-3,A549 and HeLa cell lines in vitro.Compared with the pyrrolopyrazinone（10a） and 5-fluorouracil（5-FU）,nearly all the tested compounds showed significantly-improved antitumor activities.The most promising compounds 12e and 12k（IC50=0.25 and 0.88 μmol/L） respectively show activities of 123and 35 times that of compound 10a（IC50=30.74 μmol/L） against HeLa cell line.The result reveals that the presence of chalcone moiety is beneficial to their activity and selectivity.