含异唑啉环的含能热塑性弹性体的合成及性能研究

以聚3-硝酸酯甲基-3-甲基氧杂环丁烷(PNIMMO)和3-异氰酸丙烯为原料,二月桂酸二丁基锡为催化剂,合成端烯丙基氨酯聚3-硝酸酯甲基-3-甲基氧杂环丁烷(AUPNIMMO),将AUPNIMMO与四甲基对苯二腈氧化物(TTNO)通过缩合反应得到含异唑啉环的含能热塑性弹性体。采用傅里叶变换红外光谱仪、核磁共振氢谱仪、凝胶渗透色谱仪和差示扫描量热仪对产物的结构和性能进行了研究。结果表明,含能热塑性弹性体热稳定性良好(最大热分解峰峰温217.3℃),力学性能优异,拉伸强度为4MPa,延伸率为500%。

竞争性α-氨基-3-羟基-5-甲基-4-异噁唑丙酸受体拮抗剂研究进展

α-氨基-3-羟基-5-甲基-4-异噁唑丙酸(AMPA)受体是游离型谷氨酸受体,广泛分布于中枢神经系统,介导快速兴奋性突触传递。越来越多的证据表明,其在突触可塑性及中枢敏化中发挥重要作用,并且与神经系统疾病关系密切。过度刺激AMPA受体产生兴奋性毒性会导致神经元损伤,引发癫痫、肌萎缩侧索硬化和帕金森病等一系列神经系统疾病的发生。竞争性AMPA受体拮抗剂能够有效下调AMPA受体活性,对预防和治疗神经系统疾病意义重大。本文对竞争性AMPA受体拮抗剂的研究进展进行综述。

紫罗兰酮生物碱异唑衍生物的合成及其抗肿瘤转移活性研究

目的设计并合成紫罗兰酮生物碱异唑类衍生物,结合活性筛选,发现具有活性的新型紫罗兰酮生物碱衍生物。方法制备(R)-紫罗兰酮,在此基础上经过11步有机合成反应制备紫罗兰酮生物碱异唑衍生物。目标衍生物经核磁共振波谱和高分辨质谱表征其化学结构。通过乳腺癌细胞趋化迁移实验筛选衍生物的抗肿瘤转移活性。结果共制备8个目标衍生物,经抗肿瘤转移活性筛选发现,化合物12c活性同Ion-31a相当,强于阳性对照化合物PI3K抑制剂LY294002。结论所有目标衍生物均为新化合物,其中苯甲腈取代异唑化合物12c具有显著抗肿瘤转移活性。

含哌啶结构的异唑啉类化合物的合成与杀虫活性研究

[目的]设计、合成一系列新型含有哌啶结构的异唑啉类化合物,以发现新的优良杀虫活性化合物。[方法]采用亚结构拼接原理设计合成含有哌啶基团的异唑啉类化合物。以4-乙酰基-2-甲基苯甲酸为起始原料,经9步反应合成目标化合物,并经核磁表征验证其结构。[结果]合成12个异唑啉类化合物。初步室内杀虫活性测试结果:当质量浓度为100 mg/L时,化合物3e、3f、3h和3j对小菜蛾防效为100%;当质量浓度为2.5 mg/L时,化合物3i和3j对朱砂叶螨的防效在90%以上。

氟雷拉纳的合成及其杀虫活性测定

为了探索兽药氟雷拉纳在防治农业害虫方面的应用前景,以4-溴-2-甲基苯甲酸为起始原料,经过7步反应制备得到氟雷拉纳,其结构经1HNMR、13CNMR和ESI-MS确证,反应总收率为31.11%(以4-溴-2-甲基苯甲酸计),产物纯度为98%。对氟雷拉纳进行杀虫活性测定,结果表明:在氟雷拉纳质量浓度1.25 mg/L条件下,其对小菜蛾(Plutella xylostella)、黏虫(Mythimna seperata)的杀虫活性可达100%,明显优于对照药剂四氯虫酰胺。因此,氟雷拉纳可作为先导化合物进行深入研究。

一种高效制备硝基乙酸酯的方法

异唑为母核的化合物具有多种生物活性,如抗癌、抗菌、抗病毒、抗炎、镇痛等。硝基乙酸酯是制备异唑类化合物重要的原料,报道了一种新型的硝基乙酸酯类化合物的通用合成方法,共合成4个硝基乙酸酯类化合物。其中以3-羟基丙腈和2,2,6-三甲基-1,3-二氧(杂)芑-酮为原料,经亲核取代、缩合、氧化3步反应得到硝基乙酸-3-丙腈酯,其结构经IR、^(1)HNMR、^(13)CNMR和HR-MS确证,总产率为71.6%。新的合成方法具有操作简单、成本低廉、反应条件温和等优点,适合工业化生产。

Improved Synthesis of Fructose-Derived 1, 3, 4-Oxadiazole as Novel Antitumor Agents

Aim To optimize the reaction condition for preparation of 3-spiro-1, 3, 4-oxadiazole substituted fructose and hydrolysis of its isopropylidenes stepwisely. Methods Cyclohexane was added to the reaction mixture every 8 h to remove acetic acid at 90 ℃. The isopropylidenes were hydrolyzed in 80% AcOH at 60 ℃ stepwisely in a reaction time- dependent manner. Results The yields of cyclization products 1b and 1c were improved from 53% and 51% to 74% and 79% respectively. The 1, 2-di-O-isopropylidene product 3 was obtained after 1 h and the total deprotected product 4 was obtained after 3 h in 80% AcOH at 60 ℃. Conclusion The yield of 1 is improved by cyclohexane-aided azeotropic removal of AcOH from the reaction mixture. Deprotection of 1 in 80% AcOH at 60 ℃ gives 3 or 4 after different time periods.

Theoretical Study on Reaction Mechanism of Tautomerization of Indazole and 3-halogeno-indazole

The molecular structures of indazole and 3-halogeno-indazole tautomers were calculated by the B3LYP method at the 6-311G^＊＊ level, both in the gaseous and aqueous phases, with full geometry optimization. The geometry and electronic structure of the tautomers of indazole, 3-halogeno-indazole and their transition states were obtained. The Onsager solvate theory model was employed for the aqueous solution calculations. The results of the calculation indicated that the N1-H form of the studied molecule is more stable than that of the N2-H form. The influences of the different 3-halogeno and solvent effects on the geometry, energy, charge and activation energy were discussed. The reaction mechanism of the tautomerization of indazole and 3-halogeno-indazole was also studied and a three-membered cyclic transition state of the tautomer reaction has been obtained.

Molecular Epidemiology of Oxacillin-resistant Staphylococcus aureus and in vitro Activity of Glycopeptides against Staphylococcus species

The purpose of this subject was to investigate molecular epidemiology of oxacillin-resistant Staphylococcus aureus (MRSA) isolated from hospitalized patients, and to survey the in vitro activity of teicoplanin, vancomycin and other 9 antibiotics against Staphylococcus species . MRSA were detected by oxacillin-NaCl-containing screen agar. The homology of nosocomial MRSA from ICU and RCU was determined by pulse-field gel electrophoresis. Agar diffusion, E test and agar dilution were used to compare the in vitro activity of teicoplanin and vancomycin against Staphylococcus spp from 2001 to 2003 at Peking Union Medical College Hospital. WHONET-5.3 software was used to analyze the antimicrobial susceptibility data. From 2001 to 2003, the prevalences of MRSA were 56.5%, 65.3%, 64.7%, respectively. PFGE found most of MRSA from ICU and RCU were closely related. All of S.aureus and S.epidimidis isolates were susceptible to teicoplanin and vancomycin from 2001 to 2003. However, 1 isolate of S.haemolyticus was resistant and 9 isolates intermediate to teicoplanin. The minimal inhibitory concentration of teicoplanin did not correlate well with zone diameter, when inoculum increased by 100 folds, the zone diameters of teicoplanin decreased more greatly than those of vancomycin. In 2002, severe outbreaks caused by MRSA strains had been found in ICU and RCU wards. Teicoplanin and vancomycin had good activity against clinical isolates of Staphylococci spp . Teicoplanin was less active than vancomycin against S.haemolyticus . Most of S.haemolyticus isolates were intermediate to teicoplanin. Antimicrobial susceptibility testing of teicoplanin was influenced by the diffusion speed in the agar and inoculum size.

Crystal Structure of 3-(4-nitro-) phenylsulfonyloxyisothiazole NO_2C_6H_4SO_3C_3H_2NS

C9H6N2O5S2 is monoclinic, space group P21/n, for 1278 observed reflections . The result indicates clearly the sul-fonylation takes place at oxygen. According to the data of bond lengths, the isothiazole ring displays aromaticity in some way.

SOLID PHASE SYNTHESIS OF ISOXAZOLINES

The solid-phase synthesis of isoxazolines on 2-polystyrylsulfonamidoethanol resin is reported. 2-Polystyrylsulfonamidoethanol resin 1 was reacted with acryloyl chloride to afford 2-polystyrylsulfonylamidoethyl acrylate resin 2, which was further reacted with brominated aldoximes by [3+2] cycloaddition to give isoxazoline resin 4. Resin 4 was treated with aqueous 6 mol/L HCl solution to obtain isoxazolines in good yield and purity.

New Synthesized （3-（3,4-dimethoxyphenyl）isoxazole-5- yl） Methanol as Corrosion Inhibitor on Steel in 1 M HCI

The inhibition of corrosion of steel in molar hydrochloric acid solution by new synthesized DMI （（3-（3,4-dimethoxyphenyl）isoxazole-5-yl） methanol） compound is studied by weight loss and electrochemical polarization measurements. The two methods give consistent results. The polarization curves indicate that the DMI compound acts as mixed-type inhibitor. This compound is efficient inhibitor. The inhibition efficiency increases with the increase of inhibitor concentration to reach 96% at 10-3 M for DMI. The temperature effect on the corrosion behavior of steel in 1 M HCI with and without the DMI compound at 10-3 M is studied in the temperature range from 298 to 318 K. The adsorption of inhibitor on the steel surface is found to obey the Frumkin adsorption isotherm model. From the adsorption isotherm, some thermodynamic data for the adsorption process （f, K and △Gads） are calculated and discussed.

Antimicrobial Susceptibilities of Salmonella spp. Isolated from Chicken Meat Samples

The aim of this study was to determine presence of Salmonella spp. in chicken meat samples collected from Ankara, Turkey and determine the susceptibility of the Salmonella isolates to some antimicrobial agents. For this purpose, 127 chicken samples were collected from local markets. Investigation of Salmonella was done according to horizontal method, the guidelines of the method recommended by International Standards Organization （ISO）. Antimicrobial susceptibilities of Salmonella spp. was performed with microdilution method according to the guidelines of CLSI M100-SI8. Ampicillin, gentamicin sulphate, ofloxacin, levofloxacin, ciprofloxacin, enrofloxacin, tetracycline, ceftriaxon, amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole were used in the study. Salmonella spp. was isolated from 5 （3.94%） of the 127 chicken meat samples. Although our findings are not within Turkish Food Codex （TFC） values, lower number of samples that involve Salmonella spp. indicates an improvement in the hygienic conditions in Turkey. Among 5 isolates, one isolate was sensitive to all antimicrobial agents tested. 2 isolates exhibited multidrug resistance. Successfully, all the isolates were sensitive to quinolones as a good result in spite of the reported reduced susceptibility from different regions of the world. However, this study should be improved with more chicken samples and Salmonella spp. isolate numbers to support these results.

Prevalence and Antimicrobial Susceptibility of Listeria spp, in Dairy Food Products and Water Samples in Dhaka, Bangladesh

A total of 57 samples, of which 17 were surface water samples and 40 were dairy food samples （raw milk, pasteurized milk, icecream, sweet, milk based drink like matha and borhani） were tested for the isolation ofListeria spp. Putative Listeria isolates were identified by conventional microbiological tests and Analytical Profile Index. Overall prevalence ofListeria spp. in both food and water samples were 8.77%, of which one was （1.75%） Listeria monocytogenes, 2 （3.5%） were Listeria innocua and 2 were （3.5%） Listeria welshimeri. When compared between two types of samples, water samples contained two Listeria spp. （11.76%） of which one was pathogenic Listeria monocytogenes and the other was Listeria innocua. In case of food samples, three Listeria spp. （7.5%） were isolated of which one was Listeria innocua （icecream sample） and two were Listeria welshimeri （icecream sample and raw milk）. No Listeria was found in pasteurized milk, sweet, matha and borhani. Antibiotic resistance profile of the Listeria isolates showed that 60% isolates were resistant to Ampicillin and Erythromycin, 20% isolates were Sulphamethoxazole and Ciprofloxacin resistant. No resistance was observed to Chloramphenicol for any Listeria isolates.

A COMPARISON OF THE EFFECTS OF THE PROPOFOL VERSUS MIDAZOLAM DURING TOTAL INTRAVENOUS ANESTHESIA FOR GYNECOLOGICAL SURGERY PROCEDURES

The effects of propofol and midazolam as an intravenous anesthetic were compared in 40 ASA Ⅰ-Ⅱ patients undergoing gynecological surgery during total intravenous anesthesia (TIVA). They were divided into propofol group (Pn= 20) and midazolam group (Mn= 20) randomly. The anesthesia was designed for each group respectively. Here, we discuss the experimental method and the results, which indicate that propofol is not only an effective anesthetic but also has more rapid and head-clear recovery properties than midazolam.

ab Initio Calculation on Tautomerism of Pyrazolin-5-ones

The relative stability of tautomers on pyrazolin-5-ones in gas phase and in solution is studied theoretically by STO-6-31G** +CI ab initio method and the reaciton field continuum model. the results obtained in our work are more reasonable than those by other theoretical methods and agree well with experiments.

Design, synthesis, and in vitro activity of methylisoxazole/isothiazole amides as BACE1 inhibitors

Based on the structure of compound B51（IC_（50） = 37.4 μM）, which was discovered as hit in a previous virtual screen, a series of methylisoxazole/isothiazole amide derivatives were designed and synthesized as BACE1 inhibitors. The methoxyphenylpyrimidone fragment of B51 was transformed into a methoxyphenylmethylisoxazole/isothiazole moiety to reduce the molecular weight while retaining the ability to fit into the S1＇ and S2＇ subpocket of BACE1 as predicted by docking studies. The effects of BACE1 inhibition and the structure-activity relationships were analyzed. Among all 20 designed compounds, 5t exhibited almost 10-fold improved potency（IC_（50） = 5.33 μM） compared to B51 in the BACE1 inhibition assay. Additionally, it has exhibited ＂rapid binding, slow dissociation＂ kinetics in SPR analysis, suggesting a longer inhibitory effect than B51. All acquired methylisoxazole/isothiazole derivatives were small in size and safe to normal cells, which allow them represent a novel scaffold for BACE1 inhibitor design.

Synthetic promoters consisting of defined cis-acting elements link multiple signaling pathways to probenazole-inducible system

Probenazole （3-allyloxy-l,2-benzisothiazole-1,1-dioxide, PBZ）, the active component of Oryzemate, could induce systemic acquired resistance （SAR） in plants through the induction of salicylic acid （SA） biosynthesis. As a widely used chemical inducer, PBZ is a good prospect for establishing a new chemical-inducible system. We first designed artificially synthetic promoters with tandem copies of a single type of cis-element （SARE, JERE, GCC, GST1, HSRE, and W-box） that could mediate the expression of the tS-glucuronidase （GUS） reporter gene in plants upon PBZ treatment. Then we combined different types of elements in order to improve inducibility in the PBZ-inducible system. On the other hand, we were surprised to find that the cis-elements, which are responsive to jasmonic acid （JA） and ethylene, also responded to PBZ, implying that SA, JA, and ethylene pathways also would play important roles in PBZ＇s action. Further analysis demonstrated that PBZ also induced early events of innate immunity via a signaling pathway in which Ca2＋ influx and mitogen-activated protein kinase （MAPK） activity were involved. We constructed synthesized artificial promoters to establish a PBZ chemical-inducible system, and preliminarily explored SA, JA, ethylene, calcium, and MAPK signaling pathways via PBZ-inducible system, which could provide an insight for in-depth study.

Cobalt(Ⅱ) coordination polymers built on isomeric dipyridyl triazole ligands with pyromellitic acid:Synthesis,characterization and their effects on the thermal decomposition of ammonium perchlorate

Three new cobalt（II） coordination compounds, [Co（3,3＇-Hbpt）2（H2pm）（H20）2]＇2H20 （1）, [Co（4,4＇-Hbpt）（pm）0.5（H20）]＇3H20 （2） and [Co（3,4＇-Hbpt）（pm）0.5（H20）3]＇2H20 （3） （3,3＇-Hbpt = 3,5-bis（3-pyridyl）-lH-1,2,4-triazole; 4,4＇-bpt = 3,5-bis（4-pyridyl）- 1H-1,2,4-triazole, 3,4＇-Hbpt = 3-（3-pyridyl）-5-（4＇-pyridyl）-lH-1,2,4-triazole and Hapm = pyromellitic acid） have been synthe- sized by hydrothermal reactions. Single-crystal X-ray diffraction reveals that compound 1 has a one-dimensional （1D） chain network, 2 exhibits a four-connected three-dimensional （3D） structure with 1D open channels encapsulated by water molecules, while 3 displays a regular two-dimensional （2D） architecture connected through 1D metal helical chains. In addition, the effi- cacy of compounds 1-3 as additives to promote the thermal decomposition of ammonium perchlorate （AP） is explored by dif- ferential scanning calorimetry （DSC）.