水杨酰芳胺类化合物的设计、合成及体外抗肿瘤活性研究

根据骨架迁跃原理,设计并合成了一系列具有酪氨酸激酶抑制剂拉帕替尼(Lapatinib)和诺拉替尼(Neratinib)结构片段的水杨酰芳胺类化合物,其结构均经IR,1H NMR,13C NMR和MS确证.采用四甲基偶氮唑盐(MTT)法考察所合成化合物的体外抗肿瘤细胞(A549,MCF-7,SGC-7901,Bel-7402)活性.结果表明,所合成的化合物对4种肿瘤细胞增殖均有一定的抑制活性,部分化合物的活性强于阳性对照药吉非替尼(Gefitinib).     

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。     

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。     

熊果酸C-3,C-28位衍生物的合成及其抗肿瘤活性研究

以天然产物熊果酸为原料,经过氧化、酰化、酯化等反应合成了11个未见报道的熊果酸衍生物,其结构经过MS、1H NMR及元素分析确定。以氟尿嘧啶和吉非替尼为阳性对照药,经MTT法对A549和SGC-7901细胞进行初步体外抗肿瘤活性研究。结果表明,目标化合物对两种细胞株的抑制率均明显高于母体化合物,且化合物4b和5a的抑制效果高于阳性对照药,值得进一步研究。     

6-位修饰的吉非替尼衍生物合成及细胞毒活性研究

以2-氨基-4,5-二甲氧基苯甲酸为起始原料,经关环,选择性脱甲基,醋酸酐保护,氯代,与3-氯-4-氟苯胺取代,去保护得到关键中间体4-(3-氯-4-氟苯胺)-7-甲氧基-喹唑啉-6-醇.再经过6-位羟基成醚、成酯反应合成了共计23个吉非替尼衍生物.所有目标化合物通过IR,1H NMR,13C NMR,HRMS等结构确证.并采用四甲基偶氮唑盐(MTT)法对所得目标化合物进行了细胞毒活性测试,结果发现部分化合物具有一定的抑制活性,其中化合物7b,7c,7d,8a,8m抑制人非小细胞肺癌细胞(A549)增殖活性和化合物7c,8m抑制人肝癌细胞(Hep G-2)增殖活性与吉非替尼相当.     

盐酸埃罗替尼的合成工艺改进

探索了一条全新的盐酸埃罗替尼的公斤级合成路线。以2-氨基-4,5-双(2-甲氧基乙氧基)苯甲酸乙酯为起始原料,经甲酰胺环合,POCl_3氯化,最后与间乙炔苯胺胺化后成盐制得盐酸埃罗替尼,总收率72.9%,纯度99.84%,其结构经~1H NMR、~(13)C NMR、 IR和MS(ESI)确证,并探讨了中间体和目标化合物合成工艺的影响因素。     

盐酸埃罗替尼的的合成工艺改进

探索了一条全新的盐酸埃罗替尼的公斤级合成路线。以2-氨基-4,5-双（2-甲氧基乙氧基）苯甲酸乙酯为起始原料,经甲酰胺环合,POCl₃氯化,最后与间乙炔苯胺胺化后成盐制得盐酸埃罗替尼,总收率72.9%,纯度99.84%,其结构经¹H NMR、¹³C NMR、IR和MS(ESI)确证,并探讨了中间体和目标化合物合成工艺的影响因素。      

积雪草酸衍生物的合成及抗肿瘤活性研究

以天然产物积雪草酸为起始原料,对其C-2、C-3、C-23位羟基、C-11位氢、C-28位羧基进行结构改造,合成了13个新的积雪草酸衍生物,其结构经MS及1H NMR等确证。采用MTT法,选用高表达人癌细胞(He La、Hep G2和BGC-823)对它们进行初步的体外抗肿瘤活性研究,结果表明,所测化合物对He La、Hep G2和BGC-823肿瘤细胞的抑制活性均明显强于积雪草酸,其中化合物I4和II4对He La、Hep G2和BGC-823细胞表现出很强的抑制活性,明显高于已上市药物吉非替尼,值得进一步研究。     

无溶剂研磨法合成3-取代色满-4-酮衍生物及其抑菌活性研究

以6-卤代或未取代色满-4-酮为原料,在碱催化的条件下采用无溶剂研磨法与醛发生缩合反应,合成一系列新型的3-取代色满-4-酮衍生物3a~3t,并通过IR、1H NMR、13C NMR、HRMS对所合成的化合物进行结构表征。抑菌活性测试结果表明,所合成的化合物对大肠杆菌、枯草杆菌、金黄色葡萄球菌均有不同程度的抑菌活性。     

新型苯丙烯酰氨基酸化合物的设计合成及生物活性（英文）

依据药效团的拼合策略,以上市药瑞巴派特为先导化合物,设计并合成了一系列具有苯丙烯酰氨基酸结构化合物,其结构均经~1H NMR、~(13)C NMR和MS确证.用Elisa法测定目标化合物对LPS诱导的RAW264.7细胞释放IL-6和TNF-α的抑制活性.结果显示所设计化合物显示出良好的抑制活性,其中有4个化合物的活性明显优于瑞巴派特.     

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%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

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.     

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.     

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.     

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.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.