基于配体结构的Grb2-SH2抑制剂的结构优化:更高的活性、更少的电荷、更低的肽性

生长因子受体结合蛋白2(Grb2)在致癌基因Ras活化的信号传导通路中起着关键作用,目前被广泛认为是抗肿瘤药物设计的优秀靶标.对Grb2-SH2抑制剂的研究进展进行了综述,主要针对关键残基磷酸酪氨酸的高电荷性和多肽结构的低生物相容性两个缺陷,基于天然配体与Grb2-SH2相互作用的结构特征,围绕提高活性和简化结构开展的系统构效关系和合理结构优化研究,为进一步开发磷酸酪氨酸介导的Grb2-SH2抑制剂成为新型抗肿瘤药物提供结构和理论基础.     

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在本文中, 令为一列行为混合随机变量阵列. 本文研究了行为混合随机变量阵列加权和的极限行为, 并且一些新的完全收敛性结果被取得, 这些结果推广和改进了相应的已有定理.     

生态平衡制约下离散尺度结构种群的最优收获

研究基于扩展Leslie投影矩阵的离散尺度结构种群模型的最优收获问题,约束条件包括生态平衡和开发成本等.运用凸优化理论证明了最优收获策略的存在性,导出了最优收获模式,应用模型参数给出了收获比率.结论显示:最优策略具有两阶段结构.     

Synthesis and Herbicidal Activities of Sodium Hydrogen 1-(Substituted Phenoxyacetoxy)Alkylphosphonates

Abstract

A series of sodium hydrogen 1-(substituted phenoxyacetoxy) alkylphosphonates was designed and synthesized. The test for herbicidal activity indicated that most of the phosphonates (8) possessed excellent postemergence herbicidal activities against broadleaf weeds. Especially, 8f and 8g showed the best herbicidal activity against rape and amaranth with more than 95% inhibitory rate.

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Synthesis and Herbicidal Activity of [(Substituted Phenoxyacetoxy) (Substituted Phenyl)Methyl](Methyl) Phosphinates Containing Fluorine

Abstract

A series of [(substituted phenoxyacetoxy)(substituted phenyl)methyl](methyl)phos- phinates containing fluorine were designed and synthesized. All the synthesized compounds were identified by elemental analysis, IR, ¹H NMR, mass spectrometry. O-methyl [(2-fluorophenoxyacetoxy)(2,4-dichlorophenyl)methyl](methyl)phosphinate was further analyzed by X-ray single-crystal diffraction. Their herbicidal activity against a set of weed species was examined. Some of the compounds showed potential herbicidal activity, which provided some indications for further studies on structure modification.

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Synthesis and Herbicidal Activities of 2-Methylpropan-2-Aminium Methyl 1-(Substituted Phenoxyacetoxy) Alkylphosphonates

Abstract

A series of 2-methylpropan-2-aminium methyl 1-(substituted phenoxyacetoxy) alkylphosphonates were selectively synthesized by reacting the corresponding dimethyl 1-(substitutedphenoxyacetoxy)alkylphosphonates with an excess of 2-methylpropan-2-amine. All the title compounds were identified by IR, ¹H NMR, and ³¹P NMR, some of them were further analyzed by ¹⁹F NMR and ¹³C NMR. Their herbicidal activity was investigated and the results showed that most of the demethylated aminium salts exhibited notable herbicidal activities against Brassica napus L. and Echinochloa crusgalli.

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The Synthesis and 31P NMR Spectral Studies of Cyclophosphazenes

A modified method for preparing large-scale quantities of pure hexachlorocyclophosphazene (N₃P₃Cl₆) and octachlorocyclotetraphosphazene (N₄P₄Cl₈), phosphorus pentachloride with ammonium chloride, in the presence of zinc chloride, has been developed. The time of the reaction and the quantities of the catalyst are also studied. It is found that the optimum reaction time is 1.5 h and by-products are remarkably reduced by addition of 10% zinc chloride. As indicated by the ³¹ P NMR spectra, the synthesis and separation of cyclophosphazenes can be accomplished in moderate yield of tetramer (39%) and good yield of trimer (83%).     

Synthesis and Characterization of Side Group-Modified Tetradentate Cyclotriphosphazene Derivatives

Abstract

A series of novel side group-modified cyclotriphosphazene derivatives were synthesized by the reaction of hexachlorocyclotriphosphazene [N₃P₃Cl₆] with 2,2′-diphenol and the potassium salt of 4-hydroxybenzaldehyde, and subsequent reduction of aldehyde groups to alcohol groups by the use of sodium borohydride. The bromination reaction was carried out with PBr₃ to give N₃P₃(O₂C₁₂H₈) (p-BrCH₂-C₆H₄-O-)₄. This compound was employed in reactions with macrocyclic polyamides, imidazole, or morpholine to produce title compounds. The target compounds were characterized by ¹H NMR, ³¹P NMR, ¹³C NMR, and electrospray ionization mass spectrometry.

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