含香豆素结构的1,4-戊二烯-3-酮类衍生物的合成及生物活性

为了开发新型抗肿瘤药物候选分子,将香豆素单元有机融入1,4-戊二烯-3-酮分子骨架中,设计合成了16个结构新颖的单羰基姜黄素衍生物.在确证目标分子结构后,采用甲基四氮唑盐(MTT)比色法测试了其对胃癌SGC7901细胞和肝癌HepG2细胞体外增殖的抑制活性.生物活性测试结果表明,绝大多数目标分子均能显著抑制SGC7901和HepG2细胞的体外增殖.其中,化合物4c和4j对SGC7901细胞的半数抑制浓度(IC50)为0.22和0.27μmol/L,其活性显著优于对照药剂表柔比星(1.23μmol/L).同时,化合物4l对HepG2细胞的IC50值(0.47μmol/L)也显著优于表柔比星(2.30μmol/L).细胞形态学研究结果进一步证实,含香豆素结构1,4-戊二烯-3-酮衍生物能显著抑制多种肿瘤细胞的体外增殖,可作为高效抗肿瘤药物候选分子进行深度开发.     

4-二甲氨基黄酮衍生物的合成及其活性评价

设计合成了10个4-二甲氨基黄酮衍生物,产物结构均经1H NMR,ESI-MS和元素分析确认.采用噻唑蓝(MTT)法测试了化合物对HepG2(人肝癌细胞)的抑制作用,结果表明目标化合物在30μmol/L浓度下对HepG2细胞损伤均有一定的抑制作用,大部分化合物优于对照药物槲皮素,其中化合物5c,5e,5f和5j活性最强,抑制率分别为91.0%,90.1%,95.7%和92.1%,而且化合物5f在10μmol/L浓度下对HepG2的抑制率为93.1%,具有深入研究的价值.     

3-腙喹唑啉酮衍生物的合成及抗肿瘤活性研究

通过活性拼接原理在喹唑啉酮3-位引入腙结构,使用简单的合成路线合成了一系列3-腙喹唑啉酮衍生物.目标化合物结构经核磁共振波谱(¹H NMR,¹³C NMR)和高分辨质谱(HRMS)进行了表征确证.抗肿瘤活性测试结果表明,该类化合物对A549、PC-3、Hep G2、K562等肿瘤细胞系均表现出有效的抑制活性;其中(E)-N-((2-氯-1-甲基-1H-吲哚-3-基)亚甲基)-2-(7-氟-4-氧喹唑啉-3(4H)-基)乙酰肼(H1)对Hep G2细胞的IC₅₀值为(9.90±1.13)μmol/L,(E)-2-(7-氟-4-氧喹唑啉-3(4H)-基)-N-((2-吗啉代-1-丙基-1H-吲哚-3-基)亚甲基)乙酰肼(H2)对PC-3细胞的IC₅₀值为(10.70±0.78)μmol/L,抑制活性均优于阳性对照药吉非替尼[IC₅₀=(23.33±4.14)μmol/L,IC₅₀=(12.02±5.39)μmol/L].细胞凋亡、4’,6-联脒-2-苯基吲哚(...     

含1,3,4-噻二唑、硫醚、酰胺的1,3-二取代吲哚酮衍生物的设计、合成及抗肿瘤活性研究

以吲哚酮为先导化合物,设计合成了20个含1,3,4-噻二唑、硫醚、酰胺的1,3-二取代吲哚酮衍生物.采用噻唑蓝(MTT)试验法测试目标化合物的体外抑制肿瘤细胞生长活性,测试结果表明:部分目标化合物对人肝癌细胞Hep G2、人转移胰腺癌细胞As Pc-1和人宫颈癌细胞Hela表现出良好的抑制活性;其中N-(5-((2-氟苄基)硫基)-1,3,4-噻二唑-2-基)-3-(2-氧代-3-((对-甲苯基)亚氨基)二氢吲哚-1-基)丙酰胺(6l)和N-(5-((2-甲基苄基)硫基)-1,3,4-噻二唑-2-基)-3-(2-氧代-3-((对甲苯基)亚氨基)二氢吲哚-1-基)丙酰胺(6p)对He PG2、As Pc-1和Hela细胞的IC50分别为(11.47±0.01)、(2.43±0.05)和(1.91±0.06)μmol/L;(14.32±0.01)、(1.61±0.04)和(2.77±0.05)μmol/L,其抑制活性均优于阳性对照吉非替尼[(16.41±0.05)、(5.19±0.02)和(7.89±0.05)μmol/L].     

4-取代-1-(2-甲基-6-(吡啶-3-基)-烟酰)氨基脲类衍生物合成与生物活性研究（英文）

经分子杂交技术合成了一系列4-取代-1-(2-甲基-6-(吡啶-3-基)-烟酰)氨基脲类衍生物.采用噻唑蓝(MTT)比色法研究了目标化合物对人肝癌细胞(QGY-7703)、人肺癌细胞(NCl-H460)和乳腺癌细胞(MCF-7)的体外抗肿瘤活性.1-(2-甲基-6-(吡啶-3-基)烟酰基)-4-(2,4,6-三氯苯基)氨基脲(4n)显示了最优的活性,其半数抑制浓度(IC_(50))为8.89～11.45μmol/L.细胞体内的生物研究显示,4n药物处理能明显增加细胞体内PARP切割水平以及诱导QGY-7703肿瘤细胞的凋亡.     

含脲砌块的4-氨基喹唑啉衍生物的设计、合成及抗肿瘤活性研究（英文）

为了寻找新的具有靶向治疗作用的抗肿瘤药物,设计并合成了一系列新型的含脲砌块的4-氨基喹唑啉类衍生物,并采用噻唑蓝(MTT)法测定目标化合物对MCF-7(人乳腺癌细胞)、MGC-803(人胃癌细胞)、SW620(人结肠癌细胞)、A549(人肺癌细胞)四种肿瘤细胞的抗肿瘤活性.结果显示大部分化合物具有较好的抗肿瘤活性,其中2-((4-((3,4,5-三甲氧基苯基)-氨基)喹唑啉-2-基)-硫代)-N-((3,4,5-三甲氧基苯基)氨基甲酰基)乙酰胺(10p)对MGC-803、SW620和A549三种细胞显示出最好的抗肿瘤活性, IC_(50)值分别为(7.02±0.46)、(6.00±0.78)和(7.04±1.11)μmol·L~(-1),其抗肿瘤活性和阳性对照品吉非替尼相当.分子对接结果显示,化合物10p能与EGFR很好地结合,有可能成为潜在的抗肿瘤药物.     

环氧合酶-2/5-脂氧合酶(COX-2/5-LOX)双重抑制剂吲哚-2-酰胺衍生物的合成及其抗增殖活性（英文）

设计并合成了一系列新的吲哚-2-酰胺衍生物作为环氧合酶-2/5-脂氧合酶(COX-2/5-LOX)双重抑制剂,并评估了它们的抗增殖活性.其中,(5-氯-1-(4-氟苄基)-1H-吲哚-2-基)(4-(4-甲氧基苄基)哌嗪-1-基)甲酮(12h)对人结肠癌细胞(HCT-116)、人胃癌细胞(SGC-7901)和人非小细胞肺癌细胞(A549)的抑制活性强于塞来昔布;(5-氯-1-(4-甲氧基苄基)-1H-吲哚-2-基)(4-(4-甲氧基苄基)哌嗪-1-基)甲酮(7b)对A549 (IC_(50)=6.47μmol·L~(-1))和HCT-116 (IC_(50)=13.80μmol·L~(-1))细胞表现出显著的抗增殖活性.化合物7b作为抗增殖实验中最具潜力的化合物,显示出良好的COX-2(IC_(50)=85.04nmol·L~(-1))和5-LOX (IC_(50)=125.3 nmol·L~(-1))抑制活性.对接分析表明,吲哚环上的取代基有利于改善化合物与酶的亲和力.进一步的研究证实7b可以剂量依赖性地诱导A549细胞凋亡.     

4-对丙烯基苯氨基喹唑啉衍生物的合成及抗肿瘤活性研究

以3-羟基苯甲腈为原料,经过6步反应(醚化、硝化、还原、甲脒的形成、环化和取代)合成了两个新型4-对丙烯基苯氨基喹唑啉衍生物4-[4-(E)-丙烯基苯氨基]-6-[2-吗啉基乙氧基]喹唑啉和4-[4-(E)-丙烯基苯氨基]-6-[3-吗啉基丙氧基]喹唑啉。化合物的结构经IR、HRMS、1H NMR和13C NMR确认。以人结肠癌细胞(SW480)、人肺癌细胞(A549)、人皮肤鳞状细胞癌细胞(A431)为模型,采用MTT法对所得化合物进行了体外抗肿瘤活性评价。结果表明,两个化合物均具有一定的抗肿瘤活性。特别是化合物4-[4-(E)-丙烯基苯氨基]-6-[3-吗啉基丙氧基]喹唑啉对所试肿瘤细胞均表现出良好的生长抑制活性(IC50:10.0~18.2μmol/L),与临床使用药物吉非替尼的活性(IC50:4.1~18.5μmol/L)相当。     

新型1,3-二取代酞嗪酮类衍生物的合成及抗肿瘤活性研究

为了寻找高效低毒的抗肿瘤药物,设计并合成新型的1,3位取代酞嗪酮类化合物.采用噻唑蓝(MTT)法对目标化合物在MCF-7(人乳腺癌细胞)、PC-3(人前列腺癌细胞)、SW-620(人结肠癌细胞)和HGC-27(人胃癌细胞)四种人类癌细胞的抗增殖活性进行评价.结果显示大部分化合物具有较好的抗增殖活性.其中,2-(4-(4-溴苯基)-1-氧代酞嗪-2(1H)-基)-N-(2-氟苯基)乙酰胺(5g)对MCF-7细胞的抗增殖活性较好,IC50值为6.01μmol/L,为抗肿瘤药物的研究提供了思路.     

17-(2′,5′-二取代噁唑基)-雄甾-4,16-二烯-3-酮的合成及抗肿瘤活性研究

以4-雄烯二酮1为原料,用金催化甾炔法设计并合成了一系列17-(2′,5′-二取代噁唑基)-雄甾-4,16-二烯-3-酮衍生物4a~4k.所合成产物通过1H NMR,13C NMR,IR和HRMS方法进行了结构表征.以阿比特龙为阳性对照,通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法测试了目标化合物对MCF-7(人乳腺癌细胞)、A549(人肺癌细胞)、Bel-7402(人肝癌细胞)、Hela(人宫颈癌细胞)和PC-3M-1E8(人前列腺癌细胞)的体外抗肿瘤活性.结果表明大多数化合物表现出了较好的抗肿瘤活性,其中化合物4c,4g,4i和4j的抗肿瘤活性与阳性对照物阿比特龙相当,且所测化合物对MCF-7有较好选择性作用,其IC50值在3.0~25.5μmol/L之间.     

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.