Synthesis,antifungal activity and in vitro mechanism of novel 1-substituted-5-trifluoromethyl-1H-pyrazole-4-carboxamide derivatives

Inspired by the wide application of amides in plant pathogens, a series of novel 1-substituted-5-trifluoromethyl?1H?pyrazole-4-carboxamide derivatives were designed and synthesized. Bioassay results indicated that some target compounds exhibited excellent and broad-spectrum in vitro and certain in vivo antifungal activities. Among them, the in vitro EC₅₀ values of Y₁₃ against G. zeae, B. dothidea, F. prolifeatum and F. oxysporum were 13.1, 14.4, 13.3 and 21.4 mg/L, respectively. The in vivo protective activity of Y₁₃ against G. zeae at 100 mg/L was 50.65%. SAR analysis revealed that the phenyl on the 1-position of the pyrazole ring was important for this activity. An antifungal mechanism study of Y₁₃ against G. zeae demonstrated that this compound may disrupt the cell membrane of mycelium, thus inhibiting the growth of fungi. These mechanistic study results were inconsistent with those for traditional amides and may provide a novel view for deep study of this series of pyrazole carboxamide derivatives.     

3-取代苄氧基-6-取代氨基哒嗪衍生物的合成及其除草活性

通过3-取代苄氧基-6-氟哒嗪在75～80 ℃与二甲胺的绝对无水乙醇溶液封管反应, 或在回流条件下分别与吗啡啉或哌啶反应, 合成一系列新颖的3-取代苄氧基-6-取代氨基哒嗪类化合物, 它们的结构均经IR, ¹H NMR和元素分析确证. 初步的除草活性测定结果表明, 该类化合物具有一定的除草活性, 讨论了它们的结构与除草活性的关系.     

凝血酶抑制剂的结构与活性的关系

应用了一种新的预测酶－配体复合物亲和性的方法来研究凝血酶抑制的结构－活性关系。凝血酶－抑制剂复合物的三维结构模板化合物的晶体结构进行搭建，然后使用程序ＳＣＯＲＥ计算复合物的亲和性。共分析了３个系列３４个抑制剂分子。计算所得的复合物的解离常数与实验值吻合得很好，大大优于用分子力学所给出的结果。通过比较其中两个抑制分子的结构和活性，说明了此方法能够定量给出配体分子中每个原子对结合过程的贡献大小，给出十     

Facet diagrams for quantum similarity data

The objective of this work is to demonstrate that an appropriate treatment of quantum similarity matrices can reveal hidden data grouping related to relevant structural features and even to biological properties of interest. Classical scaling is used here to extract the information contained in the similarity relationships between the elements of a molecular set. Facet theory is invoked to relate, in a qualitative way, the spatial regions to structural characteristics as well as to properties of interest. Two application examples are discussed: the Cramer steriod set and a benzene, toluene and xylene derivatives set.     

氨基乙内酰脲类BACE1抑制剂的特征结构与作用机制

对BACE1抑制剂的研究与开发已成为目前治疗阿尔兹海默症的主要研究方向之一。本文选取105个氨基乙内酰脲类BACE1抑制剂作为研究对象,借助比较分子相似性指数(Comparative Molecular Similarity Index, CoMSIA)和分子对接方法,建立定量构效关系预测模型,研究影响化合物抑制活性的特征结构信息,揭示该类抑制剂与靶标之间的作用模式。结果表明,模型(Q_²=0.45, R_²ncv=0.87, R_²pre=0.85)具有较强的预测能力,抑制剂主要占据了靶标的S3、S1和S2"位点,其主要作用力类型为氢键力。实验所得模型和信息可为日后研究开发新型高效的BACE1抑制剂提供一定的理论指导,节省研究时间与费用。     

酚类化合物的多元回归分析及神经网络法研究

在药物分子设计的诸多参量中，化合物在正辛酸／水中的分配系数的对数lgP是广为应用的一个参量（称为流水性参数）．lgP反映了化合物分子脂溶性的大小·药物分子具有适当的lgP值才能发挥最大的活性·lgP值的实验测定虽然并不困难，但对干至今仍未测定lgP值的化合物或在药物分子     

N,N-二甲基-2-溴苯乙胺类衍生物对大鼠生物活性的三维构效关系研究

N,N-二甲基-2-溴苯乙胺类衍生物是一类有效的肾上腺素阻断剂, 具有较高的生物活性. 通过比较分子力场分析(CoMFA)方法, 建立了22个标题化合物对大鼠阻断活性的三维定量结构-活性关系(3D-QSAR)模型. 该模型显示立体场、静电场对生物活性贡献分别为67.3%, 32.7%, 其中立体场与受体之间的相互作用是造成阻断剂生物活性差别的主要因素. 此3D-QSAR模型的交叉验证系数q²＝0.862, 传统的相关系数(非交互验证系数)R²＝0.962. 该模型给出的预测值与实验值非常接近, 其方差比F＝503.7, 估计标准误差(S)为0.11. 根据CoMFA模型的立体场、静电场三维等值线图不仅直观地解释了结构与活性的关系, 而且为进一步设计高活性的标题化合物提供一定的理论依据.     

Integration of genetic virtual screening patterns and latent multivariate modeling techniques for QSAR optimization based on combinations and/or interactions between peptides and proteins

Both the concept and the model of snug quantitative structure-activity relationship (QSAR) were pro-posed and developed for molecular design through constructing QSAR based on some known mode of receptor/ligand interactions. Many disadvantages of traditional models can be avoided by using the proposed method because the traditional models only determined upon molecular structural features in sample sets themselves. A genetic virtual screening of peptide/protein combinations (GVSPPC) is proposed for the first time by utilizing this idea to examine peptide/protein affinity activities. A genetic algorithm (GA) was developed for screening combinative targets with an interaction mode for virtual receptors. GVSPPC succeeds in disposing difficulties in rational QSAR,in order to search for the ligand/receptor interactions on conditions of unknown structures. Some bioactive oligo-/poly-peptide systems covering 58 angiotensin converting enzyme (ACE) inhibitors and 18 double site mutation residues in camel antibody protein cAb-Lys3 were investigated by GVSPPC with satisfactory results (R 2 cu>0.91,Q 2 cv > 0.86,ERMS=0.19-0.95),respectively,which demonstrates that GVSPPC is more inter-pretable in the ligand-receptor interaction than the traditional QSAR method.     

Synthesis and Antitumor Activities of 26-O-tert-Butyldimethylsiliyl Protodisogenyl β-D-Glucopyranoside

It was well known that natural products are an excellent source of chemical structures with a broad range of promising pharmaceutical properties, including antitumor activity1. Saponins, a group of secondary metabolites presented in a wide variety of plan…