2D-QSAR Studies on Anthranilic Acid Derivatives: A Novel Class of Allosteric Inhibitors of Hepatitis C NS5B Polymerase

Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.

Synthesis and fluorescence properties of Tb(Ⅲ) complexes with pyridine-2,6-dicarboxylic acid derivatives

Two novel ligands named 4-styrylpyridine-2,6-dicarboxylic acid (4-SPDA) and 4-(4-(2-(2, 6-dicarboxypyridin-4-yl)- vinyl)styryl)pyridine-2,6-dicarboxylic acid(DSPDA) and their complexes with Tb(Ⅲ) were synthesized and characterized by infrared spectrometry, 1H nuclear magnetic resonance, elemental analysis and gas chromatograph-mass spectrometry. The ligand synthetic route was optimized. The fluorescence properties of the complex in solid state, in different kind of solvents and in solutions with different pH values were investigated in detail. The results show that the yields of DSPDA and 4-SPDA reach over 78% by Wittig-Horner reaction and other eight pyridine-2, 6-dicarboxylic acid derivatives with different substituents on pyridine ring, and their complexes with Tb(Ⅲ) are also obtained. The fluorescence intensities of the complexes with electron-donating groups are more intense than those of the complexes with electron-withdrawing groups on pyridine ring; fluorescence intensities of the complexes are the strongest in neutral solution (pH=7), and the less the dipole moment of solvent molecule is, the stronger the fluorescence intensity is. It is found that the two ligands (4-APDA and DSPDA) are the good sensitizers for Tb(Ⅲ) ion.

2D-QSAR Studies on Phenoxybenzoic Acid Derivatives: A Novel Class of 5a-Reductase Inhibitors

The quantitative structure-activity relationship （QSAR） of 14 phenoxybenzoic acid derivatives was studied by ab initio method at the HF/6-31G level using Guassian03 software. The optimized structures together with some characteristic and electric parameters of the title compounds were obtained; some stereo-parameters were calculated by HyperChem software. Stepwise multiple regression and principal component regression methods are adopted to establish multi-parametric models between biological activity and parameters. The results indicated that the lager Ehomo, M, V and LogP, the smaller Etumo and S, and the higher biological activity. A theoretical direction was provided to synthesize some compounds with high activity.

STUDIES ON THE SYNTHESIS OF D-GLUCURONIC ACID DERIVATIVES OF 2-BUTOXY-5-FLUORO-3H-4-PYRIMIDONE AND THEIR ANTICANCER ACTIVITIES

2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementary analysis,IR spectra and ~1HNMR.

γ-Mo_(2)N/C催化剂的合成及其甲酸脱氢性能研究

甲酸(FA)因其H含量较高(4.4%)、易产H_(2)、可经小平台化合物合成等优势受到广泛关注,而γ-Mo_(2)N/C对FA沿H_(2)和CO_(2)路径分解具有非常高的选择性,产生CO极少,显示出较高的应用价值。基于此,本研究采用对苯二胺和钼酸铵水溶液经前驱体制备γ-Mo_(2)N/C催化剂,并对其FA分解性能进行了原位评价,采用热重分析(TG)、X射线衍射(XRD)、傅里叶变换红外光谱(FT-IR)、扫描电镜(SEM)、透射电镜(TEM)等表征手段对催化剂的结构和表面官能团进行了分析,利用DFT对FA在γ-Mo_(2)N (200)晶面的吸附构型进行了计算,在此基础上,对催化剂性能及FA在其表面的分解机理进行了研究。结果表明,γ-Mo_(2)N/C在较低温度下即可表现出极高的催化活性,提高γ-Mo_(2)N在C载体上的分散性能有效改善FA转化率。对苯二胺与钼酸铵的物质的量比为4∶1时,催化性能最佳,在160℃、100 h的FA分解实验中,催化剂性能稳定、H_(2)选择性高(N_(2)40 mL/min, CO<5.0×10^(-5))。而DFT计算表明,FA中O-H键的H原子与γ-Mo_(2)N/C (200)晶面上N原子结合的可能性更大,而C=O键的O原子更有可能与γ-Mo_(2)N/C (200)晶面上Mo原子结合。上述结果有助于明确FA在γ-Mo_(2)N/C作用下的分解机理,也显示出非贵金属催化剂γ-Mo_(2)N/C在FA分解制H_(2)方面潜在的应用前景。

马铃薯三糖甘草次酸衍生物通过抑制SARS-CoV-2进入靶细胞作为潜在的小分子新冠病毒融合抑制剂

目的 研究马铃薯三糖甘草次酸衍生物能否通过抑制SARS-CoV-2进入靶细胞,作为潜在的小分子新冠病毒融合抑制剂。方法 以天然SARS-CoV-2进入抑制剂甘草酸为先导化合物,利用活性亚结构的拼合原理等设计并合成了系列马铃薯三糖甘草次酸衍生物。利用SARS-CoV-2假病毒体外细胞感染模型,检测该系列甘草次酸衍生物的体外抗SARS-CoV-2活性;利用表面等离子共振技术及假病毒模型寻找先导化合物1b的抗病毒作用靶点;利用SARS-CoV-2 S蛋白介导的细胞-细胞融合体系,检测先导化合物1b是否作用于SARS-CoV-2病毒入侵宿主的膜融合过程;基于分子对接与定点突变技术,确定先导化合物1b与S蛋白的作用模式等。结果 先导化合物1b对SARS-CoV-2奥密克戎假病毒有显著抑制作用,EC50值为3.28μmol/L(P<0.05),对其它SARS-CoV-2变异株假病毒有广谱抗病毒活性。细胞-细胞膜融合实验显示1b能够抑制合胞体的形成。分子对接预测先导化合物1b可与S1与S2亚基交界处的空腔中的Glu309、Ser305、Arg765、Lys964等多个保守氨基酸残基产生氢键作用,亲和力为-8.6 kcal/mol。化合物1b在10、5、2.5、1.25μmol/L时对Arg765、Lys964、Glu309和Leu303突变后的假病毒的抑制活性显著降低(P<0.01)。结论 马铃薯三糖甘草次酸衍生物能够靶向作用于S蛋白,特异性干扰病毒-细胞膜融合阶段,继而发挥抗SARS-CoV-2感染的作用,是一类结构新颖的小分子SARS-CoV-2融合抑制剂。

One Novel 2D Co(Ⅱ) Polymer with 1,2,3-Triazole Derivative: Crystal Structure, Fluorescence and Hirshfeld Surface Analysis

One new polymer [Co（L）（H2O）2]n（1） was synthesized by 4-（ethoxycarbonyl）-5-methyl-1H-1,2,3-triazole-1-carboxylic acid（Emtc） under the in situ solvent thermal reaction（H2L = 1-（carboxymethyl）-5-methyl-1H-1,2,3-triazole-4-carboxylic acid）. The title complex performs a wave-like 2D framework and the ligand H2L demonstrates the coordination mode as μ4-η-2：η-1η-1：η-1. The crystal structure has been established by single-crystal X-ray diffraction, and characterized by FT-IR. Fluorescent property was investigated in this work. Hirshfeld surface analysis has also been carried out on 1, and obvious main intermolecular interactions are observed.

A new pyrrolidone derivative from Pistacia chinensis

A new N-phenyl-pyrrolidone derivative had been isolated from Pistacia chinesis Bunge. Its structure was elucidated as 4-hydroxy-5-（2-oxo-1-pyrrolidinyl）-benzoic acid, named pistaciamide on the basis of the 1D-NMR, DEPT, HMQC and HMBC spectroscopic techniques. 2007 Xi Kui Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Quantum Chemical Studies on the Corrosion Inhibition of Mild Steel by Piperidin-4-One Derivatives in 1 M H₃PO₄

The corrosion inhibition properties of 2,6-diphenylpiperidin-4-one (DPP) (1A) and 2,6-diphenyldihydro-2H-thiopyran-4(3H)-one (DPDT) (1B) for mild steel in 1 M phosphoric acid were studied using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopic techniques. The effect of temperature on the corrosion behavior of mild steel has been examined in the temperature range 303 - 328 K. The inhibition efficiency increases with increasing inhibitor concentration but decreases with increasing temperature. Potentiodynamic polarization studies indicated the mixed nature of inhibitors. The adsorption of the inhibitors on mild steel surface obeyed the Langmuir adsorption isotherms. The density functional theory (DFT) at the B3LYP/6- 31G (d) basis set level was performed on 1A and 1B to investigate the correlation between molecular structure and the corresponding inhibition efficiency (%). The quantum chemical parameters such as EHOMO, ELUMO, the energy gap (E), hardness (η), softness (S), dipole moment (μ), electron affinity (A), ionization potential (I), the absolute electronegativity (χ), the fraction of electron transferred (N), electrophilicity index (ω), the back-donation (EBack-donation) and Mulliken population analysis have been calculated.

Synthesis and Crystal Structure of α-(3-Phenylureido)-α-(2,4-Dichlorophenyl) Methyl Phenylphosphinic Acid

The crystal structure of a (3-phenylureido)-a (2, 4-dichlorophenyl)methyl phenylphosphinic acid, C20H17Cl2N2O3P, Mr= 435. 25,which was obtained bydesulphurisation of cis-3, 4-dipheny1-5- (2, 4-dichlorophenyl ) -1, 3, 4-diazaphospholidin2-thione-4-oxide utilizing Ag+ -H2O system in a yield of 89%, is reported. It crystallizes in orthorhombic space group Pca21 with a= 11. 286(2), b= 20. 601 (4) f c=8. 695(2)A, V= 2021 (1) A3, Z= 4, D.= 1. 430 g/cm3, p=4. 21 cm-1, F(000) =896.The final R factor is 0. 040 and Rw is 0. 045 for 946 unique observed reflections[I>3a(I)]. The result of X-ray analysis indicates that the molecules in the crystal are linkedtogether by the O(3 ) ...H (2d) - N (2d ) intermolecular hydrogen-bondings.

A Facile Synthesis of 9,10-Dimethoxybenzo[6,7]- ox-epino[3,4-<i>b</i>]quinolin-13(6<i>H</i>)-one and Its Derivatives

A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.

A Lewis acid-catalyzed tandem reaction enabling 2-arylglycerol derivative as a versatile 1,3-biselectrophile for the synthesis of 4H-chromenes and 2-pyridinones

Acid-catalyzed tandem reactions were established by employing a novel class of 2-arylglycerol derivative,5-aryl-1,3-dioxan-5-ol,as versatile 1,3-biselectrophile.In the reactions,5-aryl-1,3-dioxan-5-ol works like atropaldehydes or 2-aryl malondialdehydes,and can react with 2-naphthols andβ-keto amides,allowing the synthesis of 4H-chromenes and 5-aryl-2-pyridinones.High yields,good functional group tolerance,broad substrate scope and simple reaction operation make this protocol attractive.

新型2-酰基氰基乙酸类衍生物SYP-10898的研究

以对叔丁基氯苄为起始原料,经氰化、酯化、酯交换和酰基化4步反应合成了新化合物2-酰基氰基乙酸酯类衍生物SYP-10898,其化学结构经核磁共振氢谱和元素分析确证。室内生物活性测试结果表明,SYP-10898对朱砂叶螨Tetranychus cinnabarinus成螨的LC50值为3.67mg/L,优于对照药剂丁氟螨酯(cyflumetofen)。田间试验结果表明,在50mg/L剂量下,SYP-10898对柑桔红蜘蛛Panonychus citri表现了良好的速效性和持效性,3d后的防效在93%以上,30d后的防效在79%以上。

微波辐射下2-芳氧甲基苯并咪唑-1-丙腈衍生物的合成

在微波辐射下,以无水碳酸钾为催化剂,经芳氧基苯并咪唑的aza-Michael加成反应合成了一系列2-芳氧甲基苯并咪唑-1-丙腈衍生物.经元素分析、IR、1 HNMR和13 CNMR对其进行了表征,用单晶X射线衍射测定了化合物4e的晶体结构.结果表明,化合物4e属三斜晶系,晶胞参数a=1.041 3(3)nm,b=1.592 7(4)nm,c=0.995 1(3)nm,α=90°,β=111.007(15)°,γ=90°,V=1.540 7(7)nm3,Z=4,F(000)=672.晶胞堆积发现化合物通过分子间氢键和π-π相互作用自组装成了一维链状超分子结构.

Yb(OTf)_3催化下用研磨法合成喹喔啉-2,3-二酮衍生物

将邻苯二胺衍生物、草酸以及催化剂Yb(OTf)3置于研钵中,不加任何溶剂,在室温下进行固相研磨,以较高的产率得到产物喹喔啉 2,3 二酮衍生物。该法反应条件温和,操作简便,且对环境友好。

用2-(4,5-二甲基-2-噻唑偶氮)-5-二甲氨基苯甲酸作显色剂导数光度法同时测定钴和镍

本文研究了用2-(4,5-二甲基-2-噻唑偶氮)-5-二甲氨基苯甲酸(简称DMTAMB)作显色剂,在乙醇介质中,利用一阶导数消除钴(Ⅲ)和镍(Ⅱ)彼此间的干扰,对镍矿石中微量钴和镍进行同时测定,结果满意。

2-{2-[3-(取代苯基)-3-氧代-2-1,2,4-三唑-1-基-丙基]-苯基}-2-甲氧亚氨基乙酸甲酯和乙酰甲胺类衍生物的合成与杀菌活性研究

以2-甲基苯甲酰甲酸甲酯为起始原料,通过与甲氧基胺的盐酸盐、甲胺、N-溴代丁二酰亚胺(NBS)和1H-1,2,4-三氮唑钠反应合成了两个系列共计22个2-{2-[3-(取代苯基)-3-氧代-2-1,2,4-三唑-1-基-丙基]-苯基}-2-甲氧亚氨基乙酸甲酯和乙酰甲胺类的衍生物.经IR,1HNMR和MS对目标化合物进行了结构表征.用浓度为10μg?mL-1的目标化合物进行了初步离体杀菌活性试验,结果表明:Ha4,Ha5,Ha7对油菜菌核病有杀菌活性;Ha2,Hb8对小麦纹枯病有杀菌活性;Hb4对蔬菜灰霉病有杀菌活性;Hb4,Hb5对小麦赤霉病和小麦纹枯病均有杀菌活性.

毛细管气相色谱法分离2-苯基羧酸酯对映体

手性2-芳基羧酸酯是制备手性非甾体抗炎药物2-芳基羧酸的重要的中间体,为了建立可用于2-苯基羧酸酯对映体分离的手性毛细管气相色谱法(CGC),分别使用2,6-二-O-戊基-3-O-丁酰基-β-环糊精及2,6-二-O-苄基-3-O-庚酰基-β-环糊精作毛细管气相色谱手性固定相,研究了其对2-苯基丁酸甲酯、2-苯基丁酸乙酯、2-苯基丁酸异丙酯、2-苯基丙酸甲酯及2-苯基丙酸环戊酯等5种2-苯基羧酸酯对映体的分离能力。结果表明,用2,6-二-O-戊基-3-O-丁酰基-β-环糊精及2,6-二-O-苄基-3-O-庚酰基-β-环糊精作手性固定相的毛细管气相色谱法可以分离2-苯基丁酸甲酯、2-苯基丙酸甲酯和2-苯基丙酸环戊酯对映体。2,6-二-O-戊基-3-O-丁酰基-β-环糊精对3种2-苯基羧酸酯对映体的分离能力超过了2,6-二-O-苄基-3-O-庚酰基-β-环糊精。