作为杀菌和杀虫先导的1,2,4-噁二嗪衍生物的设计与合成研究（英文）

噁二嗪片段常用于小分子的修饰和构象限制,同时噁二嗪也是一种理想的酰胺电子等排体.基于商品化琥珀酸脱氢酶抑制剂杀菌剂的结构框架,通过生物电子等排手段,以噁二嗪替换酰胺结构,设计并合成了24个1,2,4-噁二嗪类化合物.生物活性测试结果表明,在400mg/L浓度下,大部分化合物对黄瓜霜霉病表现出较好的活性.此外,在600mg/L的浓度下,这些化合物对粘虫的致死率达到100%,说明噁二嗪的结构值得作为先导继续研究,进而发现活性优异的新化合物.     

氰基在药物分子设计中的应用

含氰基药物在临床治疗药物中占有相当比重.将氰基基团引入到小分子药物中是药物化学结构改造的重要研究策略之一.综述了氰基在药物分子设计中的应用,氰基的引入可以调节小分子药物的物理化学特性,改变小分子的药代动力学性质,提高药物的生物利用度;通过氢键相互作用、共价相互作用、偶极相互作用以及π-π相互作用增强配体与靶标蛋白的相互结合能力以及对其它靶标蛋白的选择性;同时,氰基是羰基、卤素等多种官能团的生物电子等排体;将氰基引入到药物小分子当中,可以通过阻断易代谢位点进而提高药物代谢稳定性等.     

氟喹诺酮-3-N-酰胺类衍生物的合成与抗肿瘤活性

为扩展氟喹诺酮由抗菌活性向抗肿瘤活性转化的结构修饰策略,利用药效团生物电子等排及其拼合和骨架迁越药物化学分子构建方法,以酰胺基作为氟喹诺酮C-3位羧基的生物电子等排体,氟喹诺酮骨架为酰胺基的功能修饰基,设计合成了氟喹诺酮-3-N-酰胺类目标化合物。其结构经元素分析和光谱数据确证。体外抗肿瘤实验结果表明,目标化合物对Hep-3B细胞和Capan-1细胞的抗增殖活性均显著强于母体环丙沙星的活性,尤其对Hep-3B细胞的抑制活性最强。因此,用酰胺基来替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。     

磺酰基在药物分子设计中的应用

含磺酰基药物在临床治疗药物中占有相当比重,将磺酰基引入到小分子中是药物分子结构改造的重要策略之一,综述了磺酰基在药物分子设计中的应用.就结构而言,磺酰基和羰基、羧基、四氮唑、磷酸基具有相似的大小和电荷分布,可以作为它们的生物电子等排体而引入到小分子中,从而保持或增强小分子的生物活性;磺酰基具有独特的物理化学性质,磺酰基的引入可以调节小分子的溶解性和酸碱性;磺酰基能提供两个氢键受体,合理的引入磺酰基可以通过增加小分子和作用靶标的氢键相互作用而提高化合物的生物活性;磺酰基结构较稳定,引入磺酰基可以通过阻断易代谢位点而提高药物代谢稳定性,延长其作用时间,提高其生物利用度,从而改善小分子的药代动力学性质;磺酰基属于极性基团,磺酰基的引入还可以增加小分子的极性从而降低h ERG毒性.     

药物设计中的生物等排取代与先导化合物的展开

本文叙述了年来在药物设计中应用广泛的“生物等排取代”这一方法的概念、发展历史及其具体应用，说明了生物等排取代在先导化合物的展开中的重要作用。     

镍催化偕二氟烯烃的不对称氢硅化反应

<正>含氟类化合物在农药、医药以及材料科学等领域有着广泛的应用[1-3],而含二氟甲基结构的化合物则是其中的佼佼者.在药物设计过程中,二氟甲基可以作为羟基以及巯基的电子等排体替代原有的基团[2].此外,二氟甲基上的碳氢键具有一定酸性,可以作为氢键供体与酶或者蛋白质上的氢键受体发生相互作用,从而增强药物分子的选择性以及生物活性.引入二氟甲基还可以提高分子的代谢稳定性、脂溶性以及生物利用率,     

砜亚胺酰胺的研究进展

砜亚胺酰胺是磺胺的氮杂类似物,同砜亚胺一样具有较高的稳定性、良好的理化性质、结构的多样性以及多种氢键受体和供体的作用.同时,氮取代基的改变可调节化合物的生物活性和物理化学性质.药物化学工作者用其代替磺胺或羧酸片段应用于先导化合物的优化中,发现该结构表现出较好的活性,而且不同的构型发挥着不同的作用.本文概述了砜亚胺酰胺的...     

益母草碱类似物设计、合成及其Na+/H+交换器-1抑制活性

以中药益母草中有效成分益母草碱为先导化合物,按生物电子等排原理,设计合成了18个益母草碱类似物.通过MS,1H NMR,13C NMR对化合物结构进行表征.初步的药效研究结果表明部分化合物具有Na+/H+交换器-1 (NHE-1)抑制活性,其中化合物1a和1e的活性显著强于阳性对照药Cariporide.     

镍氢催化的迁移脱氟烯烃偶联:由三氟甲基取代的烯烃构建偕二氟烯烃

正偕二氟烯烃是羰基化合物的生物电子等排体,与酮、醛、酯类化合物有着相似的空间位阻和电子效应,但却具有更好的代谢稳定性~([1]).因此,偕二氟烯烃作为一类重要的含氟化合物,被广泛应用于农药、医药、材料化学等领域中~([2]).例如,当青蒿素中的羰基转化为偕二氟烯烃后,该青蒿素类似物的药物活性提高了近一倍.     

手性NADH模型的研究新进展

ＮＡＤＨ／ＮＡＤ＾＋是生物代谢过程中一种重要的辅酶。其氧化态在生物燃料分了降解过程中作为电子受体被还原；其还原态生物合成过程中作为一种绝妙的手性还原剂，为生物大分子 提供电子和自由能。     

Dichroism of absorption and polarization of phosphorescence of molecules of the closed form of nitrobenzospirothiopyran

The spectral-polarization characteristics of absorption and phosphorescence of molecules of the initial form of nitro-substituted indolinospirobenzothiopyran were studied in oriented polyethylene films and in solutions with different polarity. An oscillator model of the electron transitions responsible for the formation of absorption and luminescence spectra was suggested. It was established that the principal differences in the spectral and photophysical properties of the compound studied and its oxygen-containing analog are associated with the fact that the electronegativity of the S atom is lower than that of the O atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1143–1146, June, 1997.     

非那雄胺合成工艺改进

非那雄胺能抑制5α-还原酶的活性,明显降低二氢睾酮水平,是一种治疗良性前列腺增生的有效药品。该合成工艺以甾烯酮酸为原料,将其与氯化亚砜反应,无须分离即与叔丁胺反应得17β-酰胺化合物,再氧化开环,环合,氢化,脱氢合成了非那雄胺。经元素分析、IR、1HNMR、13CNMR、MS分析表征了其结构。该法无须使用昂贵的2,2-二吡啶二硫化物和剧毒药品苯亚硒酸酐,且以乙酸铵代替氨气,降低了对设备的要求和腐蚀,更适用于工业生产。     

Determination of heats of detonation and influence of components of composite explosives on heats of detonation of high explosives

The heats of detonation of 20 simple high explosives and explosive mixtures were determined by means of an adiabatic detonation calorimeter designed by the authors. The results indicated that the performance of the instrument was reliable and the experimental data were very accurate. For explosive mixtures, there was a linear accumulative relationship between the heats of detonation of the explosive mixture and its components. Accordingly, the heats of detonation of explosive mixtures could be calculated directly from the heats of detonation of simple explosives and the characteristic heats of other components. The experiments showed that the gold or brass shell of the cylindrical charge could be substituted by a thick-walled porcelain shell, which had the advantage of cheapness.

     

Synthesis of phenolic components of Grains of Paradise

Two vanilloids, (5E)-8-(4-hydroxy-3-methoxyphenyl)oct-5-en-4-one (1) and 4-[3-hydroxydecyl]-2-methoxyphenol (2), isolated from the dried seeds of Grains of Paradise (Aframomum melegueta), were synthesized; the latter compound was made as the S-enantiomer and the material derived from the seeds was found to be a 1:1.7 mixture of the R and S isomers. The synthetic route used should allow the preparation of analogs having extended alkyl chains and consequently different lipophilicity, and 3, a homolog of 2, was also prepared.     

Summary of development of the theory of stability of colloids and thin films

In this review, the research of the author in the field of colloidal systems is summarized. The factors influencing colloidal stability are systematized and analyzed. Examples are presented to illustrate the practical utilization of the theory of stability of colloids and thin films.This review was prepared on the basis of the works of the author, which were awarded the State Premium for 1991 in the field of science and technology, chemistry section.Institute of Physical Chemistry, Russian Academy of Sciences, 117915 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1708–1717, August, 1992.     

Study of hydration of two cements of different strengths

Main hydration products of two cement pastes, i.e. CSH-gel, portlandite (P) (and specific surface S) were studied by static heating, and by SEM, TEM and XRD, as a function of cement strength (C-33 and C-43) hydration time (th) and subsequent hydration in water vapour.Total change in mass on hydration and air drying, M_o, increased with strength of cement paste and with hydration time. Content of water escaping at 110 to 220°C, defined as water bound with low energy, mainly interlayer and hydrate water, was independent on cement strength but its content increased with (th). Content of chemically bound (zeolitic) water in CSH-gel, escaping at 220-400°C, was slightly dependent on strength and increased with (th). It was possibly derived from the dehydroxylation of CSH-gel and AFm phase. Portlandite water, escaping at 400-500°C, was independent on cement strength and was higher on longer hydration. Large P crystals were formed in the weaker cement paste C-33. Smaller crystals were formed in C-43 but they increased with (th). Carbonate formated on contact with air (calcite, vaterite and aragonite), decomposed in cement at 600-700^oC. It was high in pastes C-33(1 month) and C-43(1 month), i.e. 5.7 and 3.3%, respectively; it was less than 1% after 6 hydration months (low sensitivity to carbonation) in agreement with the XRD study showing carbonates in the air dry paste (1month), and its absence on prolonged hydration (6 months) and on acetone treatment. Water vapour treatment of (6 months) pastes or wetting-drying increased this sensitivity.Nanosized P-crystals, detected by TEM, could contribute to the cement strength; carbonate was observed on the rims of gel clusters.This revised version was published online in November 2005 with corrections to the Cover Date.     

氯氧化镁生成热的研究

用氧化镁氯化镁水溶液制备了8水合氯氧化镁[nMg(OH)2·MgCl2·8H2O], 并测定了其在盐酸中的溶解热, 实验结果表明, 氯氧化镁溶解热与n值呈线性关系, 根据溶解热求出5Mg(OH)2·MgCl2·8H2O和3Mg(OH)2·MgCl2·8H2O的生成热分别为-7727.1和5888.1kJ·mol^1^-。     

Thermodynamics of the formation of oxosulfides of rare-earth elements

The enthalpies of solution of several oxosulfides of rare-earth elements and the high-temperature enthalpies of oxosulfides and oxosulfates of lanthanum and yttrium were measured using solution calorimetry and high-temperature microcalorimetry techniques. Standard enthalpies of formation and some thermodynamic properties of oxosulfides and oxosulfates were calculated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2 pp. 294–297, February, 1997.     

恶臭嗅辨实验室建设探讨

针对恶臭测试的环境影响问题,提出了解决的实例方案,并对方案的要点及优缺点进行讨论,此方案在实际操作中具有较好的效果。