4-(1-芳基-3-氧代-5-苯基戊氨基)苯磺酰胺的合成与抗糖尿病活性初步研究

采用分段投料法, 通过Mannich反应直接合成了12个含有磺胺的β-氨基酮化合物, 收率23%～97%。所制备的新化合物采用FTIR、ESI-MS、¹H NMR、¹³C NMR和HR-MS等方法进行结构确证。初步抗糖尿病活性筛选结果显示, 所合成的含有磺胺的β-氨基酮化合物具有不同程度的抗糖尿病活性, 其中目标分子1e具有较好的α-葡萄糖苷酶抑制活性, 1l表现出较好的过氧化物酶体增殖物激活受体反应元件 (PPRE) 激动活性。在此基础上, 讨论了所得化合物的构效关系。     

α-苄基取代的琥珀酸单酰胺类化合物的设计，合成与生物活性

为寻找效果更好的降血糖药物以及进一步研究列奈类化合物的构效关系,以米格列奈为先导物,设计、合成具有降血糖活性的α-苄基取代的琥珀酸单酰胺类化合物。以丁二酸二乙酯和各种取代苯甲醛为原料,经缩合、水解得苯亚甲基丁二酸,再进行酸酐化、胺解和氢化等反应合成了12个目标化合物,化合物结构通过元素分析、IR、¹H NMR和ESI-MS得以确证,并测定了它们的降血糖活性。初步药理试验表明所合成的化合物中6c、6e和6g降糖作用较明显,其中6e较为突出,其降糖作用与那格列奈相当。
     

2-芳亚胺基-4-噻唑烷酮类化合物的合成及生物活性

目的设计、合成新的2-芳亚胺基-4-噻唑烷酮类化合物并研究其对一氧化氮合酶(NOS)的抑制活性。方法运用N-氯乙酰-1,2,3,4-四氢异喹啉或N-氯乙酰邻苯二甲酰亚胺与取代硫脲反应，简便地合成了15个新的2-芳亚胺基-4-噻唑烷酮类化合物，测试新合成的目标化合物的NOS抑制活性。结果和结论合成了15个新的2-芳亚胺基-4-噻唑烷酮类化合物，大部分反应收率大于65%。所有化合物的结构用¹H NMR，IR，MS及元素分析进行了表征。初步药理筛选结果表明，部分化合物具有NOS抑制活性。     

4-酰基-5-吡唑酮的二烃基锡配合物的合成、表征及其抗癌活性研究

目的　设计合成一系列新型有机锡化合物,通过药理筛选寻找具有抗肿瘤活性的药物并探讨其构效关系。方法　以4-酰基-5-吡唑酮为配体合成有机锡化合物,用元素分析、红外光谱、 ¹H,¹³C,¹¹⁹Sn NMR等方法对得到的化合物作结构表征并利用几种药理模型进行体外抗癌活性筛选。结果　合成了一系列R₂SnL₂ 型有机锡新配合物并确定其结构。结论　药理筛选结果表明,多个化合物(3～6,9～11)对HL-60, HCT-8, Bel-7402,BGC-823和KB癌细胞有效,显示了较强的抗癌活性。     

萘酰亚胺-多胺缀合物的合成及体外抗癌活性

合成了6个萘酰亚胺-多胺缀合物, 化合物的结构经元素分析、¹H NMR、¹³C NMR和MS确证。经MTT法对白血病细胞 (K562)、人乳腺癌细胞 (MB-231) 和前列腺癌细胞 (Ln cap cell) 进行了体外活性测试, 结果表明大多数化合物的体外抗肿瘤活性优于对照品氨萘非特 (amonafide), 其中化合物6d、6e和6f对正常人肝上皮细胞 (QSG-7701) 和肝癌细胞 (BEL-7402) 具有良好的选择性。     

喹啉酮酸类化合物的设计合成与抗HIV-1整合酶活性研究

以HIV-1整合酶为靶点, 设计并合成了8个含喹啉酮酸类新化合物, 其结构经¹H NMR和MS确证。用酶联免疫吸附剂测定法 (ELISA方法) 测定了其体外抗HIV-1整合酶活性。结果表明, 目标化合物中D-2、D-4和D-7对HIV-1整合酶的抑制活性小于100 µmol·L⁻¹, 有待对此类化合物作进一步细胞水平的活性评价。     

噻吩并四氢吡啶衍生物的合成及其抗血小板聚集活性研究

为了寻找新型的ADP受体拮抗剂类抗血栓药物, 合成了18个未见文献报道的噻吩并四氢吡啶衍生物, 化合物结构经¹H NMR和MS确证。大鼠体内抗血小板聚集活性研究表明, 化合物C1的活性优于阳性对照药噻氯匹定, 值得进一步深入研究; 化合物A4、B2、C4和C7均有不同程度的抑制血小板聚集的活性。     

非核苷类逆转录酶抑制剂的研究XVⅢ: 4-烯丙基和4-叠氮基取代的三嗪类化合物的合成及抗HIV活性

在已有工作基础上, 基于分子对接设计合成了8个新的4-烯丙基取代和4-叠氮基取代的二芳基三嗪类衍生物。抗HIV-1活性的测试结果表明所有新化合物均具有抗HIV-1活性。其中化合物7c不仅抑制HIV-1野生株的复制 (IC₅₀ = 0.034 μmol×L^-1, SI = 6 475), 且对Y181C和K103C双突变酶显示出较强的抑制活性, 其IC₅₀值为9.39 μmol×L^-1, 高于奈韦拉平。     

4-(2-乙酰氧基苯甲酰氨基) 丁酰胺衍生物的设计、合成及初步活性研究

为了寻找新型γ-氨基丁酸 (γ-aminobutyric acid, GABA) 类抗癫痫药物, 以抑制性神经递质γ-氨基丁酸受体 (GABA_R) 为作用靶点, 以GABA为原料设计合成了一类全新结构类型的4-(2-乙酰氧基苯甲酰氨基) 丁酰胺类化合物 (5a～5l), 通过IR、¹H MNR、EI-MS及元素分析确证了目标化合物的结构。初步药理活性评价结果表明, 目标化合物具有良好抗癫痫活性, 值得进一步研究, 在此基础上, 初步讨论了该类化合物的构效关系。     

3-芳基-5-三氮唑基-噁二唑衍生物HIF-1抑制剂的设计、合成与构效关系研究

目的 设计、合成3-芳基-5-三氮唑基-噁二唑类缺氧诱导因子-1(hypoxia-inducible factor 1，HIF-1)抑制剂。方法 以化合物8为先导，将吡唑基替换为1,2,3-三氮唑基，并对噁二唑和苯环取代基等进行改造，获得全新的3-芳基-5-三氮唑基-噁二唑衍生物。结果 所合成的大部分化合物均显示出较优的HIF-1抑制活性，化合物10n活性最强，IC₅₀值为0.59 μmol·L^-1，其作用机制是抑制HIF-1α蛋白表达，且能显著抑制SKOV3细胞的侵袭和迁移。结论 设计、合成的3-芳基-5-三氮唑基-噁二唑类衍生物是全新的HIF-1抑制剂，显示出抑制肿瘤迁移的效应。     

Synthesis,anti-inflammatory and antioxidant activity of ring-A-monosubstituted chalcone derivatives

A library of ring-A-monosubstituted chalcone derivatives (4a–4i, 5a and 5b) was designed and synthesised. The structures as well as the identities of these compounds were established on the basis of spectral (¹H NMR, ¹³C NMR, FT-IR and Mass) and elemental (C, H, N) analyses. All the derivatives were evaluated for their anti-inflammatory and antioxidant activities in vitro using the inhibition of protein denaturation and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, respectively. The results indicated a promising anti-inflammatory activity for most of the synthesised compounds with many derivatives showing activities similar to or greater than that of the standard. The sulphonamide-substituted chalcones 4h, 4i, 5a and 5b were found to be the most active derivatives across the concentration range tested. However, all the derivatives exhibited rather mild antioxidant activity compared to the ascorbic acid standard. Interestingly, it was observed that the unsubstituted parent chalcone was one of the optimal compounds with only the trifluoromethyl analogue 4a showing better activity as an antioxidant. The two regioisomeric aminochalcones and 4′-cyanochalcone 4b also seemed to possess decent antioxidant potential.     

Microwave-assisted CAN-catalyzed solvent-free synthesis of N-allyl quinolone-based pyrano[4,3-b]chromene and benzopyrano[3,2-c]chromene derivatives and their antimicrobial activity

A new series of pyrano[4,3-b]chromene and benzopyrano[3,2-c]chromene derivatives have been synthesized via microwave-assisted one-pot, three-component reaction of N-allyl quinolones, cyclic β-diketones, and 4-hydroxy-6-methyl-2H-pyran-2-one/4-hydroxy coumarin in the presence of catalytic amount of ceric ammonium nitrate under solvent-free condition. The protocol offers expeditious and solvent-free synthesis with excellent yield to furnish fused chromenes for their antimicrobial activity. The chemical structures of the synthesized compounds were elucidated by ¹H NMR, ¹³C NMR, FT-IR, elemental analysis, and mass spectral data. All the compounds were screened against a representative panel of pathogenic strains by broth micro dilution minimum inhibitory concentration method. Among these derivatives, compounds 6i, 6k, 6l, and 6m were found to have admirable activity when compared to the standard drugs.     

Synthesis, antimicrobial activity, and molecular modeling of novel 4-(3-(4-benzylpiperazin-1-yl)propoxy)-7-methoxy-3-substituted phenyl-2H-chromen-2-one

A series of novel 4-(3-(4-benzylpiperazin-1-yl)propoxy)-7-methoxy-3-substituted phenyl-2H-chromen-2-one (7a–7j) were synthesized by the reductive amination of 7-methoxy-3-phenyl-4-(3-piperizin-1-yl-propaxy)chromen-2-one (6) with different substituted aromatic aldehydes by using sodium cyanoborohydride in methanol. The newly synthesized compounds were purified and their structures were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy. The representative analogs were screened for in vitro antimicrobial activity. The compounds exhibited significant antibacterial and antifungal activity as that of standards. The data was further compared with structure-based investigations using docking studies with the crystal structure of oxidoreductase (1XDQ and 3QLS) protein organisms. The estimated score by genetic algorithm was found to have a good correlation with the experimental inhibitory potency of the derivatives.     

Design,synthesis and anti-acetylcholinesterase evaluation of some new pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>]-1,2,4-triazolo[1,5-<Emphasis Type="Italic">c</Emphasis>]pyrimidine derivatives

The target new hybrid molecule types pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines phosphonates 4 and 2-(coumarin-3’’-yl)-7-phenylpyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines 5 were prepared via Michaelis–Arbuzov rearrangement (Arbuzov reaction) of pyrazolotriazolopyrimidines chloride 3a–c, with trialkyl phosphate and Knoevenagel reaction of 2-cyanomethyl derivatives 3d–f with salicylic aldehyde, respectively. The precursors 3 were obtained in two steps starting from aminopyrazole 1. Target compounds 4 and 5 were completely characterized by ¹H NMR, ¹³C NMR, ³¹P NMR, IR and HRMS. The anti-acetylcholinesterase activity of compounds 4 and 5 was evaluated, and results found indicated that they have possessed significant activities (IC₅₀ = 1.73–39.86 µM), and the preliminary SAR of these compounds was investigated.     

Synthesis and antibacterial activity evaluation of 2,6-bis(6-substituted-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-3-yl)pyridine derivatives

The reaction of 5,5′-(pyridine-2,6-diyl)bis(4-amino-3-mercapto-1,2,4-triazole) with various carboxylic acid in phosphorus oxychloride yielded the corresponding 2,6-bis(6-substituted-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-3-yl)pyridine derivatives 6a–l. The structures of the newly synthesized compounds were confirmed by elemental analysis, ¹H NMR and ¹³C NMR spectral, mass spectral, and Infrared spectral studies. All the synthesized target compounds have been investigated for their in vitro antibacterial activity, and the preliminary results revealed that the compounds 6b and 6k exhibited very promising activity against Escherichia coli and Pseudomonas aeruginosa.     

A facile synthesis of new 3,3-disubstituted phthalides of pharmacological interest

A series of new phthalides of pharmacological interest were synthesized by a protocol involving condensation of two γ-keto acids, 2-(4-isopropylbenzoyl)benzoic acid (1a) and 2-(4-isopropyl-3-nitrobenzoyl)benzoic acid (1b) with phenolic compounds in the presence of catalytic quantity of concentrated sulphuric acid. The method is simple, efficient, economical and environmentally benign as the reaction is carried out under solvent free condition attempting a green approach. Structural characterization of these newly synthesized compounds was accomplished by IR, UV, ¹H NMR, ¹³C NMR, Mass spectral data, elemental analysis and chemical reactions. Some of the synthesized phthalides were found to exhibit antifungal and antibacterial activity against various human pathogenic bacterial and fungal strains.     

Zn(OTf)2-catalyzed three component, one-pot cyclocondensation reaction of some new octahydroquinazolinone derivatives and access their bio-potential

An efficient synthesis of some new octahydroquinazolinone derivatives 4a–x by the cyclocondensation reaction of corresponding 2-thi(oxo)-1,2-dihydroquinoline-3-carbaldehyde 1a–e, 1,3-dicarbonyl compounds 2a–b, and substituted urea 3a–c using zinc triflate as a catalyst in refluxing ethanol in high yield is described. The structures of new compounds have been characterized on the basis of elemental analysis, FT- IR, ¹H NMR, ¹³C NMR, and mass spectral data. All the synthesized compounds were evaluated for their antimicrobial activities against various microbes. Minimum inhibitory concentration values of all the 24 synthesized compounds were also determined. Some of the synthesized compounds exhibited excellent antimicrobial activity.     

New thiazolidine-2,4-diones as antimicrobial and cytotoxic agent

New (Z)-5-substituted-2,4-thiazolidinediones (3a–m) were easily prepared by the condensation of thiazolidine-2,4-dione (1) with suitable aldehydes (2a–m) via microwave irradiation technique. The reaction between (Z)-5-substituted-2,4-thiazolidinediones and 4-(bromomethyl) benzoic acid, using potassium carbonate as base in refluxing acetone, followed by a workup in acidic medium provided 4-(((Z)-5-substituted-2,4-dioxothiazolidin-3-yl)methyl) benzoic acid derivatives (4a–m). The structures of the newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR spectral studies, and elemental analysis. All compounds were evaluated for their in vitro antimicrobial and cytotoxic activities. Antibacterial and antifungal results revealed that most of the compounds showed significant activity where as compounds 4c and 4g are found to be broad spectrum antibacterial and antifungal properties, the MIC values were observed in the range of 2–4 and 2–8?μg/ml, respectively. In MTT cytotoxicity studies, the compound 4g was found most potent. In HeLa, HT29, A549, and MCF-7 cells, the IC₅₀ values were observed in the range of 30–36?μM.