抗肝片吸虫病药物化合物的合成及解偶联活性研究

肝片吸虫是传播极为广泛的家畜体内寄生虫。文献报道N(2,4,5三氯)苯基2羟基3,5,6三氯苯磺酰胺(简称为HBSA)及其卤化衍生物是比较好的治疗肝片吸虫病药物,部分化合物已获美国专利[1]。经我们近几年对苯磺酰苯胺类化合物药物作用机理的研究初步证实:该类化合物是线粒体氧化...     

苯并噻嗪酮类化合物抗血吸虫活性的研究

本文以苯并噻嗪酮为母核,设计合成了12个新化合物,对其进行体外抗日本血吸虫活性研究,发现化合物A5的活性较好,对日本血吸虫童虫和成虫的IC50分别为12.2μM和6.8μM。     

苦皮素的结构修饰研究

以苦皮藤中的有效杀虫成份苦皮素为原料合成了 8种衍生物 ,用元素分析、核磁共振波谱等数据对其进行了结构确证 .以 3龄虫 (mythimnaseparatawalker)为试虫 ,测定了它们的杀虫活性 .结果表明 ,苦皮素衍生物对粘虫表现程度不等的杀虫效果     

苯并硫氮杂卓类化合物作为抗血吸虫药物的研究

体外筛选实验发现:苯并硫氮杂卓类化合物B_(30),在50μM浓度时,可以完全杀灭日本血吸虫。本文以B_(30)为先导化合物,通过药物化学中的生物电子等排原理对其进行结构改造,设计并合成了11个B_(30)的类似物。对这些化合物进行体外抗血吸虫效果的评价,发现其中一个化合物A9的活性较好:其对血吸虫童虫和成虫的IC50分别为7.30μM和12.0μM,较先导化合物B_(30)IC50值降低了一倍。     

7,10—二芳基—六氢（四氢）苯并[C]吖啶—8—酮的合成

吖啶及吖啶酮类化合物具有广泛的药理活性,其中许多化合物具有明显的杀菌、抗炎、增强记忆、镇痛和抗癌等活性。如早年开发的抗癌药物山柚柑碱(Acronycine)就具有显著的抗癌作用,且抗瘤谱较广。近年来抗癌新药安吖啶(Amsacrime)在临床上用于治疗急性白血病收到疗效后,对吖啶及吖啶酮衍生物的合成及抗癌活性研究日渐增多。已测定了一些化合物     

N—三苯锗丙酰基—α—氨基膦酸酯的合成及其性质研究

合成了两个系列含有三锗丙酰基的α－氨基磷酸酯类化合物，研究了空阻大的α－氨基膦酸酯与β－三苯锗丙酸的缩合方法、反应条件及反应机理，生物活性测定结果表明，这类衍生物与相应的α－氨基膦酸衍生物相比有显著抗癌活性和抗烟草病毒活性。     

吡喃半乳糖糖基化马蹄金素衍生物的合成及抗乙肝病毒活性研究

为提高马蹄金素(MTS)衍生物的肝脏药物浓度,增强其抗乙型肝炎病毒(HBV)活性.通过以乙醇胺为连接臂将具有肝靶向性的半乳糖配基与MTS进行间接连接,设计合成了5个肝靶向MTS衍生物,通过~1H NMR,~(13)C NMR,~1H-~1H COSY,HMQC和ESI-MS对其进行了结构表征,并用Hep G2 2.2.15细胞模型初步评价了合成所得目标化合物的抗乙肝病毒活性.结果表明,所有目标化合物对HBV DNA的复制均有抑制作用,且具有一定的量效关系.     

具有肝靶向潜力的马蹄金素衍生物合成及抗乙肝活性研究

为了提高马蹄金素(MTS)衍生物在肝脏病变部位的药物浓度,增强其抗乙肝病毒活性,设计并合成了5个半乳糖糖基化修饰的具有肝靶向潜力的MTS衍生物,通过1H NMR,13C NMR,1H-1H COSY,HMQC和ESI-MS对其进行了结构表征,并用Hep G2 2.2.15细胞模型初步评价了合成所得目标化合物的抗乙肝病毒(HBV)活性.结果表明,所有目标化合物对HBV DNA的复制均有抑制作用,且具有一定的量效关系.     

双氢青蒿素衍生物的研究进展

从醚类、酯类、杂原子取代C-10-O类等单活性基团衍生物和双活性基团衍生物两大类结构出 发,综述了1997后合成的双氢青蒿素衍生物及其合成方法,在生理活性研究方面发现双氢青蒿素衍生物除具有抗疟活性外,还具有抗肿瘤、抗血吸虫、抗孕、提高免疫力等其他生物与生理活性.     

间接糖基化马蹄金素衍生物的合成及抗乙肝病毒活性研究

以二缩三乙二醇或三缩四乙二醇为连接臂, 通过间接引入具有肝靶向性的D-半乳糖配基的方法, 设计合成了6个半乳糖糖基化修饰的肝靶向马蹄金素(MTS)衍生物; 通过¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMQC和ESI-MS对其结构进行了表征; 并以HepG2 2.2.15为细胞模型初步评价了目标化合物的抗乙肝病毒(HBV)活性. 结果表明, 所有目标化合物对HBV DNA的复制均有抑制作用, 且具有一定的量效关系. 化合物15b的体外抗HBV活性最好, 后期研究将选用其进行小鼠体内组织分布实验, 并与原型化合物以及Y101体内组织分布情况进行比较研究, 以验证半乳糖基的引入能否提高MTS衍生物的肝靶向性.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.