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毒蕈碱受体激动剂的三维定量构效关系研究 总被引:1,自引:0,他引:1
采用比较分子场分析法(CoMFA)研究了55个四氢吡啶类毒蕈碱受体激动剂的三维定量构效关系(3D-QSAR), 建立了具有较强预测能力的3D-QSAR模型. 所得模型的交叉验证相关系数(q2)为0.507, 常规相关系数(R2)为0.982 , 标准方差为0.218, 说明系列化合物分子周围立体场和静电场的分布与生物活性间存在良好的相关性. 模型不仅很好地预测了训练集和测试集化合物的活性, 而且为设计活性更高的受体激动剂提供了理论依据. 相似文献
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Introduction 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1-substituted-1,3,5-triazines (Ⅰ) are dihydrofolate reductase(DHFR) inhibitors, hence they possess the inhibition to the growth of bacteria and cancer cells. Baker's antifolate (Ⅱ) has shown promise as an antitumor agertt in clinical trials. The study of the structure-activity relationships of I shows that the inhibition to vertebrate DHFR is significantly influenced by the hydrophobicity of 1-substituent, i.e., the stronger the hydrophobicity of the 1-substituent, the more potent the inhibition of the compound to vertebrate DHFR. 相似文献
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利用3D-QSAR中的比较分子力场分析法(CoMFA)研究了标题化合物的定量构效关系。通过不同探针与空间网格点间隙的对比研究,发现以 、空间网格点间隙20nm结果为最优。从 值来看,CoMFA计算得到的模型有很高的预测性。依据CoMFA系数图设计一些新化合物并预测了它们的活性,结果表明:对抑制革兰氏阳性菌有数种化合物的活性比迄今合成的化合物要高。 相似文献
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考虑药物配基与蛋白质受体的3类非键作用模式,利用蒙特卡罗随机采样技术得到了一种分子结构性质表达方法:分子表面随机采样分析(RaSMS).同时,定义了蛋白质原子探针、虚拟受体可及表面、表面随机采样目标面积逼近法等多个相关概念,在理论和算法上对该法进行了可行性分析.在此基础上,对31个标准甾体化合物进行了定量构效关系(QS... 相似文献
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GABAA受体是中枢神经系统内重要的抑制性受体,有广泛的神经生理活性.由于镇静/抗惊厥药物在临床上的广泛应用,使得其中苯并二氮杂作用位点尤为重要.我们用比较分子场法(CoMFA)对一系列咪唑苯并二氮杂类化合物(BZ)与五种重组受体亚型的亲和力进行了结构活性关系研究,得到的一组模型都有较高的交叉验证系数.并在此基础上,建立了非交叉验证的一组PLS模型.用该组模型对随机选择的6个化合物组成的测试集进行了预测,都得到了相当满意的结果,表明所建立的一组模型具有良好的预测能力.本研究对于设计高亲和力的BZ受体的配基和研究GABAA受体的模型有指导意义. 相似文献
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以已知18种多溴二苯醚(polybrominated diphenyl ethers,PBDEs)芳香烃受体结合能力实验值为因变量,构建基于取代基参数的PBDEs芳香烃受体结合能力定量构效关系模型以补足PBDEs芳香烃受体结合能力值,借助全析因实验的分析方法研究不同取代位置对PBDEs芳香烃受体结合能力的主效应及二阶交互效应,并分别从总取代基数、两苯环取代相似性、同一苯环取代基分布性综合研究PBDEs取代特征对芳香烃受体结合能力的影响规律.研究表明: PBDEs芳香烃受体结合能力受各取代位置主效应和二阶交互效应的显著影响,邻位取代基可显著降低PBDEs芳香烃受体结合能力,对位取代基则显著增强,间位取代基主效应较弱,主要通过与邻对位取代基间的二阶交互效应影响PBDEs芳香烃受体结合能力;总取代基数、两苯环取代相似性与PBDEs芳香烃受体结合能力无显著相关性,而同一苯环上取代基间分散性越大,同系物芳香烃受体结合能力越小. 相似文献
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Porous hybrid microspheres were fabricated by the synthesized calcium gluconate-g-poly(D,L-lactide) (CG-g-PDLLA) composites.These hybrid microspheres were treated with an alkaline solution for different period of time to control the amount of generated carboxylate groups and remained CG on the surface.The microspheres were then incubated in a supersaturated simulated body fluid (1,5 SBF) solution for different time to investigate their biomimetic mineralization behavior.The depositions were found to have a fine cluster morphology,a similar crystal structure and chemical structure to natural hydroxyapatite,and a medium Ca/P of approximately 1.30.The effect of surface treating time on the structure and mineralization behavior of these microspheres has been discussed in detail.The results indicate that the nucleation and growth of apatite on the surface are influenced by the induced carboxylate groups and the remained CG.The hybrid CG-g-PDLLA microspheres have the potential as a novel alternative in bone tissue engineering. 相似文献
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Bernhard Kutscher Michael Bernd Thomas Beckers Emmanuel E. Polymeropoulos Jürgen Engel 《Angewandte Chemie (International ed. in English)》1997,36(20):2148-2161
Hormones—and in particular, the sex hormones—were the first growth factors discovered to be involuntary helpers of cancer. Female breast cancer and male prostate cancer are the best known examples of tumors acknowledged to be hormone-dependent. A look at cancer statistics shows that breast cancer is still the most frequent cancer in women; in men, prostate cancer plays a similarly dominant role with increasing age. Shutting down the main production site of the sex hormones estrogen and testosterone either by removing the ovaries or by castration is a well-known and often effective therapy; however, these procedures can be problematic due to the concomittant psychological stress. Modern hormone therapy for advanced breast cancer and prostate cancer attempts to spare the patient such irreversible operative procedures for as long as possible, by using hormone antagonists, such as the LHRH antagonists, which hinder deployment of the hormone itself and thus its growth-promoting activity. 相似文献
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A multi‐channel surface acoustic wave (SAW) detection system which is employed to detect various organic molecules in a static system was prepared using 315 MHz one‐port quartz resonators and a home‐made computer interface for signal acquisition and data process. The oscillating frequency of the quartz crystal decreases on adsorption of organic molecules on the coating materials. The principal component analysis (PCA) method with SAS software was applied to select the appropriate coating materials onto the SAW crystals for organic vapors, e.g. hexane, 1‐hexene, 1‐hexyne, 1‐propanol, propionaldehyde, propionic acid, and 1‐propylamine. A dataset for a multi‐channel sensor with 19 SAW crystals for 7 analyses was collected after comparing the correlation between the 19 coating materials and the first six principal component (PC) factor. Furthermore, linear discriminate analysis (LDA) with SPSS software and a profile discrimination map were also applied and discussed for the discrimination of these organic vapors. These organic molecules could be clearly distinguished by the six‐channel SAW static sensor. The effect of concentration for various organic vapors was investigated and discussed. 相似文献
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Jacqueline Marchand-Brynaert Nathalie Jongen Jean-Luc Dewez 《Journal of polymer science. Part A, Polymer chemistry》1997,35(7):1227-1235
The surface of PVDF film was selectively modified by wet chemistry. Treatment with aqueous LiOH produced HF-elimination and the emergence of an oxygen-containing functionality. The XPS analysis clearly indicated the presence of ketone-, ether(epoxide)-, and alcohol motifs. The percentage of alcohols could be significantly increased by reduction of the ketones with NaBH4 in 2-propanol, followed by reduction of the epoxides with DIBAL-H in hexane. Thus, the full treatment led to a PVDF surface displaying 7 to 16% of oxygen-containing units, of which about 60% consisted in alcohol motifs. The reactvity of the surface-displayed hydroxyl functions was assayed by radiolabeling with [3H]-Ac2O. © 1997 John Wiley & Sons, Inc. J. Polym Sci A: Polym Chem 35: 1227–1235, 1997 相似文献
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Patrick Shahgaldian Martin Hegner Uwe Pieles 《Journal of inclusion phenomena and macrocyclic chemistry》2005,53(1-2):35-39
Heptakis 6-deoxy-6-[12-(thiododecyl) undecanamido-β-cyclodextrin has been produced by reaction of Heptakis(6-deoxy-6-amino)-β-cyclodextrin and 12-(thiododecyl)undecanoic acid using O-Benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) as activating agent. Self-assembled monolayers of this macrocycle have been
used in a surface plasmon resonance (SPR) sensor; it has been shown that this system is suitable to discriminate between d and l enantiomers of thyroxine, with a greater affinity for the d-enantiomer.
Received in final form: 6 January 2005 相似文献
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家蝇与大鼠GABA受体抑制剂的药效团模型及其3D-QSAR研究 总被引:4,自引:1,他引:4
采用DISCOtech方法,用7个大鼠γ-氨基丁酸(GABA)A受体抑制剂和11个家蝇GABAA受体抑制剂分别建立了其药效团模型;用CoMFA方法建立了22个大鼠GABAA受体抑制剂和29个家蝇GABAA受体抑制剂的3D-QSAR模型,模型的交叉验证相关系数分别为0.526和0.679,验证了药效团模型的合理性,为设计更高活性和更高选择性的化合物提供了参考 相似文献
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采用比较分子场分析(CoMFA)方法研究了一组嘧啶类衍生物酪氨酸激酶抑制剂活性与结构的关系.所得模型不仅能够很好地预报训练集中的化合物的活性,而且还可以准确地预报预报集中的化合物活性.通过分析分子场等值面图在空间的分布,可以观察到叠加分子周围的立体和静电特征对化合物活性的影响. 相似文献
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本文首次将McGreery的推广LEPS法用于异核双原子分子的吸附势能面.设CO在Ni面上的吸附位置有3种(图1).取Sato参数为0.5,所得典型的势能面示于图2、图3.当C—O键平行于表面并接近Ni面上的3种吸附位置时,各势能面均与图2类似,先进入一势阱,然后越过势垒进入第二势阱.发生解离型C及O的原子吸附时,共有4种模式.各势能面上表征吸附的参数列于表1,吸附模式见图1.在4种吸附模式中最稳定的是C模式,即对角相邻5CN上的解离双原子吸附,R_(c-o)=6.65a.u.,它是R_(c-o)(平衡)=2.17a.u.的三倍多.当CO键与表面垂直且接近Ni面上3种吸附位置时所得势 相似文献
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通过沉淀聚合方法,利用自由基共聚制备了苯乙烯-顺丁烯二酸酐共聚物(SMA),利用SOCl2的酰氯反应,在SMA大分子链上接枝聚乙二醇侧链,制备了聚苯乙烯-g-聚乙二醇(PEG-g-PS)的大分子表面改性剂。利用大分子表面改性剂在聚苯乙烯基体中具有选择性迁移扩散的特性,实现了对聚苯乙烯薄膜表面极性的改善作用。采用衰减全反射傅立叶变换红外光谱仪和表面静态接触角法检测了聚苯乙烯的表面极性。结果发现,PEG-g-PS上的聚醚链段可以有效的富集在聚合物表面,明显改善PS的表面极性和亲水性,表面极性可提高3倍,达到11.6mN/m。同时,大分子表面改性剂和聚苯乙烯基体间有一定的相容性,有效地克服了小分子表面改性剂容易流失,改性寿命较短的重要缺陷,使表面改性的持久性充分增加,实现对聚合物表面改性效果终生化的目的。而且大分子表面改性剂在极性溶剂的诱导作用下,可以实现进一步的迁移扩散,充分提高了聚苯乙烯的表面极性。 相似文献