微波辐射下水相中3,5-双亚苄基哌啶-4-酮衍生物的合成

利用微波辐射, 以碳酸钾为催化剂, 快速于水相中合成了一系列3,5-双亚苄基哌啶-4-酮衍生物, 所合成化合物的结构经红外光谱、核磁共振光谱和高分辨率质谱予以确证.     

1-取代哌啶-4-酮肟醚的合成与杀菌活性测定

以取代苄胺或苯乙胺为起始原料, 依次经Michael 加成, Dieckmann缩合, 水解脱羧, 肟化和醚化等多步反应合成了11个未见文献报道的1-取代哌啶-4-酮肟醚5a～5k. 目标化合物的结构经元素分析, IR, 1H NMR和MS测定确证. 初步杀菌活性测试表明, 部分化合物有较好的杀菌活性.     

A new application of diphenylphosphorylazide (DPPA) reagent: convenient transformations of quinolin-4-one, pyridin-4-one and quinazolin-4-one derivatives into the 4-azido and 4-amino counterparts

Herein, we describe a transformation of the oxo-function of a series of quinolin/pyridin/quinazolin-4-ones into 4-azido and thence into 4-amino derivatives in moderate yields by a very short and convenient new procedure using DPPA (diphenylphosphoryl azide) as reagent. A mechanism for this interesting new application of DPPA is suggested based on the identification of some of the intermediates.     

Synthesis,characterization and antimicrobial activities of new bis-hydrazonothioxothiazolidinone derivatives

New bis-hydrazonothioxothiazolidinone derivatives based on 2-thioxothiazolidin-4-one were synthesized in good yields using a simplified experimental condition. The structure of synthesized compounds was established with the help of common physico-chemical analysis and various spectroscopic techniques like FT-IR, mass and ¹H NMR. The results of characterizations are in good agreement with the proposed structure of all the synthesized compounds. Further, the antimicrobial (antibacterial and antifungal) activities of all the synthesized derivatives were carried out against various species like Bacillus subtilis, Escherichia coli, Aspergillous niger and Aspergillous flavus by using agar-cup method. The results of antimicrobial screening showed that all the compounds have mild to moderate activity. However, some of the compounds (3a, 3b, 3d, 3e, 3f, 3g, 3i and 3j) have shown better activity than the other.     

Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita

Abstract

A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0?mg L^?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0?mg L^?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.     

Design,synthesis and antibacterial activity of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain

A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12a, 12d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.     

Synthesis of 1,2,3-benzotriazin-4-one derivatives containing spirocyclic indoline-2-one moieties and their nematicidal evaluation

To discover new chemotypes of nematicides with proper toxicological profiles, a series of novel 1,2,3- benzotriazin-4-one derivatives were synthesized and further bioevaluated. The bioassay results showed that most of the synthesized compounds were endowed with moderate to good control efficacy against Meloidogyne incognita at 10.0 mg/L in vivo. Among them, compounds 6k and 6p displayed 100% inhibitory activities at this concentration, which implied that they could be used as lead compounds for promising nematicides.     

Synthesis and antiviral activities of novel 1,4-pentadien-3-one derivatives bearing an emodin moiety

A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/mL, which was superior to ningnanmycin (409.3 mg/mL).     

1-取代哌啶-4-酮芳甲酰腙的合成及其抗白血病活性

以取代苄胺或伯胺为原料,依次经过Michael加成、Dieckmann缩合、水解脱羧、酰腙化反应合成了10个未见文献报道的1-取代哌啶-4-酮芳甲酰腙9a～9j,化合物结构经1H NMR,IR,MS和元素分析确证.初步的生物活性测试表明,部分化合物能有效抑制白血病K562细胞的增殖,具有潜在的抗白血病活性.     

Design,synthesis and in vitro biological evaluation of novel 4-methoxy-5-hydroxycanthin-6-one derivatives as potential anti-tumor agents

Abstract

Canthin-6-one analogue, 4-methoxy-5-hydroxycanthin-6-one (CAN1) was isolated from Picrasma quassioides (D.Don) Benn., and a series of derivatives containing the CAN1 framework were designed, synthesized, and evaluated for anti-proliferative activity against two human cancer cell lines, HepG2 and HCT116. Among these compounds, the most representative compound d exhibited better anti-proliferative activities in vitro compared with the positive control Fluorouracil (5-FU), with IC₅₀ values of 5.05?μM (HepG2) and 6.65?μM (HCT116), respectively. Compound d triggered more significant HepG2 cell apoptosis than 5-FU did in a dose-dependent manner. Furthermore, western blot assay indicated that d could enhance the expression of p65 while promoting pro-apoptotic proteins and suppressing the anti-apoptotic proteins in a dose-dependent manner. All these results demonstrated that d might be a potential agent for cancer therapy deserving further exploring.     

Synthesis, antibacterial and antifungal activity of some derivatives of 2-phenyl-chromen-4-one

Some derivatives of 2-phenyl-chromen-4-one (flavone ring) have been synthesized and tested for antibacterial and antifungal activities along with their chalcone precursors against four human pathogenic bacteria and five plant mould fungi. The structures of the synthesized compounds were elucidated by UV, IR and¹H NMR spectroscopic techniques, and elemental analysis. The antibacterial and antifungal screens of the synthesized compounds were performed in vitro by the filter paper disc diffusion method and the poisoned food technique.     

吲唑衍生物及其生物活性研究进展

吲唑衍生物具有抗肿瘤、抗菌、抗炎及治疗骨质疏松等多种生物活性,因此,在药物化学领域受到广泛的关注,具有巨大研究前景及价值。本文总结归纳了近几年来与吲唑衍生物相关的文献,对单取代、双取代及多取代吲唑衍生物及其生物活性的最新研究进展进行了综述,希望能为开发高效低毒的吲唑衍生物提供一定的理论基础。     

2-氨基-4-羰基噻吩的Knoevenagel反应

在碳酸钾等无机碱的存在下,异硫氰酸酯和4-氯乙酰乙酸乙酯反应生成2-氨基-4-羰基-4,5-二氢噻吩-3-甲酸乙酯。该化合物显示了与醛基的反应活性,即Knoevenagel反应,本文对该噻吩化合物的Knoevenagel反应位点选择性进行了研究。运用Gaussian03程序对化合物进行了几何全优化和相应的电荷、轨道能量分析研究。     

An efficient synthesis of new thiazolidin-4-one fused s-triazines as potential antimicrobial and anticancer agents

As a part of our endeavor toward the synthesis of new heterocyclic bioactive agents, two series of thiazolidin-4-one fused s-triazines were synthesized by applying an efficient palladium catalyzed C–C Suzuki coupling using catalyst system Pd(OAC)₂, Xphos and K₃PO₄ as a base in toluene solvent. Moreover, the synthesized analogs were further screened for their in vitro antimicrobial as well as anticancer efficacy against prostate cancer PC3 cells. Some compounds displayed remarkable antimicrobial activity and noticeable anticancer activity. It was observed that, both benzonitrile and nicotinonitrile are essential to increase the different pharmacological activities. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and MS analysis.     

Synthesis and activities of new 4-hydroxy benzoxazolone derivatives

<正>A series of new 4-substituted benzoxazolone derivatives were synthesized according to a convenient method,their anti-inflammatory and analgesic activities in vivo were evaluated.All of them were new compounds,the structures of all the synthesized compounds were confirmed by ~1H NMR,~(13)C NMR,ESI-MS and HR-MS.Most of the compounds exhibited anti-inflammatory activity.     

Synthesis and biological evaluation of novel 1, 2, 3-benzotriazin-4-one derivatives as leukotriene A4 hydrolase aminopeptidase inhibitors

A series of novel 1,2,3-benzotriazin-4-one derivatives were designed,synthesized and their inhibitory activities against leulcotriene A_4 hydrolase aminopeptidase in vitro were evaluated.Many compounds showed moderate to good activities at the concentration of 10 μmol/L.Among them,compound Ⅳ-16 exhibited the highest inhibitory activity up to 80.6% with an IC_(50) of 1.30 ± 0.20 μmol/L The compound Ⅳ-16 was also tested the proliferation inhibitory activities in THP1 human AML cell line and its binding model with LTA_4H enzyme by molecular docking was studied.It indicated that 1,2,3-benzotriazin-4-one was a promising scaffold for further study.The relationship between structure and inhibitory activity was also preliminarily discussed.     

苯并异噻唑啉酮类衍生物合成、抑藻活性及构效关系研究

以1,2-苯并异噻唑啉-3-酮和脂肪醇为原料合成8个苯并异噻唑啉酮类衍生物。抑藻活性实验表明,当合成化合物2a~2h的浓度为2.0mg/L时,对亚心形扁藻、蛋白核小球藻和球等鞭金藻表现出良好的生长抑制活性。采用Chemoffice 2010软件构建化合物分子模型,用半经验计算方法 AM1对分子几何构型进行全优化,计算得到量子化学参数和物理化学参数。构效关系研究表明合成化合物的抑藻活性与疏水性参数Log P相关,并建立了关系模型。     

Synthesis and biological evaluation of 1,4-pentadien-3-one derivatives containing 1,2,4-triazole

A series of new 1,4-pentadien-3-one derivatives containing 1,2,4-triazole moiety were synthesized. The structures of the synthesized compounds were charactered via ¹H NMR, ¹³C NMR and HRMS. Antibacterial bioassays indicated that some of compounds showed potential antibacterial activities against Ralstonia solanacearum (Rs), Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. Citri (Xac). Compounds F₈ and F₁₇ showed good in vitro antibacterial activities against Rs, with the EC₅₀ values of 18.6 and 18.6 μg/mL, respectively, which were better than commercial agent bismerthiazol (55.2 μg/mL). Furthermore, compounds F₁₂ and F₁₅ showed good in vitro antibacterial activities against Xoo, with the EC₅₀ values of 10.9 and 17.5 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). Moreover, compounds F₂, F₉, F₁₆ and F₁₇ showed good in vitro antibacterial activities against Xac, with the EC₅₀ values of 6.6, 5.4, 7.5 and 7.8 μg/mL, respectively, which were better than commercial agent bismerthiazol (54.9 μg/mL). The effect of compound F₉ on Xac bacterial cell membrane rupture was observed by scanning electron microscopy (SEM). In addition, antiviral bioassays indicated that some of compounds showed excellent protection activities against tobacco mosaic virus (TMV). Compounds F₅ and F₁₅ showed good protecting activity against TMV, with the EC₅₀ values of 108.3 and 105.4 μg/mL, respectively, which were better than commercial agent ningnanmycin (214.7 μg/mL). Microscale thermophoresis (MST) also showed that the binding of compound F₂ to TMV coat protein (TMV-CP) yielded a Kd value of 1.260 ± 0.654 μmol/L, which was very close to ningnanmycin (1.058 ± 0.286 μmol/L). Similarly, the molecular docking studies for F₂ and F₅ with TMV-CP (PDB code: 1EI7, ID: 4QGH) indicated that compounds F₂ and F₅ had partially interacted with TMV-CP.     

Regio- and stereochemical features of the reactions of 1,2,5-trimethylpiperidin-4-one with chalcone

The reactions of N-substituted piperidin-4-ones with benzylideneacetophenone, resulting in the synthesis of a number of heterocyclic 1,5-dicarbonyl compounds, were studied. 1,2,5-Trimethylpiperidin-4-one enters into cascade-type chalcone addition accompanied by intramolecular aldol condensation giving rise to the 3-azabicyclo[3.3.1]nonane system. The conformations of the 1,5-dicarbonyl compounds and azabicyclononanes synthesized were determined; the regio- and stereochemical features of the reactions of 1,2,5-trimethylpiperidin-4-one with chalcone were studied.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2693–2697, December, 2004.     

A new reagent system for installation of an aryl group onto the monoacetate of 4-cyclopentene-1,3-diol

Among the three types of reagents from PhMgX (X=Br, Cl) and CuCN for phenylation of 4-cyclopentene-1,3-diol monoacetate, PhMgCl/CuCN (cat.) and Ph₂Cu(CN)(MgCl)₂ in THF afforded the trans-1,4-isomer efficiently (82-87% yields, 91-93% regioselectivity). Similarly, o- and p-RC₆H₄MgCl (R=Me, OMe, CH₂CH) in combination with CuCN furnished good to excellent reactivity and regioselectivity. As an application, a three-step synthesis of dihydromultifidene was accomplished successfully.