双对羟基苯甲醛Schiff碱的合成及与DNA作用

以1,4-二(3-氨基丙基)哌嗪(BAPP)与对羟基苯甲醛(PHBA)为原料,合成了含哌嗪环的双对羟基苯甲醛Schiff碱——N,N'-二(4-羟基苄基)-1,4-二(3-亚氨基丙基)哌嗪;产物结构经元素分析、红外光谱、核磁共振氢谱和紫外光谱进行确认。采用紫外吸收光谱法和黏度法研究了标题化合物与小牛胸腺DNA(CT-DNA)的相互作用,发现紫外吸收光谱出现了减色效应和红移现象,DNA的相对黏度随着化合物浓度的增大而增加,这些现象说明该双Schiff碱以插入方式与CT-DNA结合。     

N-苯基哌嗪的合成

改进了N-苯基哌嗪的合成工艺,以二乙醇胺为原料,经二氯亚砜氯化得双(β-氯乙基)胺盐酸盐,用正丁醇做溶剂,在碱存在下,与苯胺缩合制备N-苯基哌嗪,收率69.4%。     

Enantioselective Polymeric Composite Membrane for Optical Resolution of Racemic Mixtures of α-Amino Acids

The optical resolution of racemic mixtures of α-amino acids was performed using novel enantioselective polymer membrane to obtain optically pure isomers. The novel membranes were prepared by polymerizing a mixture of D-arginine, piperazine, and trimesoyl chloride in-situ interfacial on polysulfone ultrafiltration membrane. ATR-FTIR spectroscopy, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Transmission Electron Microscopy (TEM) techniques were used to characterize the membranes and co-relate membrane morphology with membranes performance. The optical resolution performance of the membrane process was quantified by performing optical resolution of racemic arginine and asparagine in pressure driven separation mode at low pressures. The influence of monomers concentrations and their ratio in the polymerizing mixture on the flux and enantioseparation was studied. The observations indicated >91 percent enantiomeric excess (>91% ee) of L-arginine and >56 percent enantiomeric excess (>56% ee) of L-asparagine in the permeate of the racemic feed. The membrane prepared using equiconcentrated (2%) solutions of D-arginine, piperazine, and trimesoyl chloride exhibited highest enantiomeric excess (91%). At 91% ee the separation factor (α) for L-arginine was approximately 16.     

Synthetic and Spectroscopic Studies of Polymeric Metal Complexes Involving 1,4-[5-Disulphonyl-8-Hydroxyquinoline]piperazine

The polymeric metal complexes of Co^II, Ni^II, Cu^II, Zn^II, Cd^II , Ce^III, La^III and UO₂ ^II with 1,4-[5-disulphonyl-8-hydroxyquinoline]piperazine have been synthesized. It has been found that the ligand coordinates to the metal ion as a bibasic tetradentate chelating agent and can form polymeric metal complexes. The structure of the isolated metal complexes is supported by chemical analysis, thermoanalytical data, and conductivity measurements, as well as uv-visible, ¹H-NMR, and IR spectroscopy. The stoichiometry of these metal complexes is M:L=2:3. A tetrahedral stereochemical configuration is suggested for the polymeric metal complexes with the exception of the Ce^III and La^III complexes, which form six-coordinate polymeric metal complexes.     

西他列汀侧链哌嗪盐酸盐制备的工艺优化

为了提高西他列汀侧链哌嗪盐酸盐的产率,并简化操作,以三氟乙酸乙酯为原料,经肼解、氧氯化磷环合、乙二胺亲核取代、闭环等反应,制备了3-(三氟甲基)-5,6,7,8-四氢[1,2,4]三唑并[4,3-α]哌嗪盐酸盐。工艺产物收率较高,反应条件温和,操作简单,溶剂回收简单。     

Optimization of Diarylthiazole B‐Raf Inhibitors: Identification of a Compound Endowed with High Oral Antitumor Activity,Mitigated hERG Inhibition,and Low Paradoxical Effect

Aberrant activation of the mitogen‐activated protein kinase (MAPK)‐mediated pathway components, RAF‐MEK‐ERK, is frequently observed in human cancers and clearly contributes to oncogenesis. As part of a project aimed at finding inhibitors of B‐Raf, a key player in the MAPK cascade, we originally identified a thiazole derivative endowed with high potency and selectivity, optimal in vitro ADME properties, and good pharmacokinetic profiles in rodents, but that suffers from elevated hERG inhibitory activity. An optimization program was thus undertaken, focused mainly on the elaboration of the R¹ and R² groups of the scaffold. This effort ultimately led to N‐(4‐{2‐(1‐cyclopropylpiperidin‐4‐yl)‐4‐[3‐(2,5‐difluorobenzenesulfonylamino)‐2‐fluorophenyl]thiazol‐5‐yl}‐pyridin‐2‐yl)acetamide ( 20 ), which maintains favorable in vitro and in vivo properties, but lacks hERG liability. Besides exhibiting potent antiproliferative activity against only cell lines bearing B‐Raf V600E or V600D mutations, compound 20 also intriguingly shows a weaker “paradoxical” activation of MEK in non‐mutant B‐Raf cells than other known B‐Raf inhibitors. It also demonstrates very good efficacy in vivo against the A375 xenograft melanoma model (tumor volume inhibition >90 % at 10 mg kg^?1); it is therefore a suitable candidate for preclinical development.     

加速溶剂提取-液相色谱法分析动物组织中的磺胺残留

目的:建立快速溶剂提取动物组织中磺胺类抗生素残留的方法,并将该方法与超声波辅助提取法、匀浆法比较。方法:以样品添加回收率为指标,探索各种提取参数的影响,优化提取条件。结果:选出了加速溶剂提取法的最适条件:二氯甲烷为提取溶剂,提取压力500psi,温度40℃,整个提取过程需时23min,提取溶剂12ml,六种磺胺的添加回收率均高于80%,相对标准偏差在9%以下。结论:加速溶剂提取与超声波辅助提取法、匀浆相比,是一种快速、高效的提取方法。     

Multi‐residue analysis of sulfonamides in animal tissues by capillary zone electrophoresis with electrochemical detection

BACKGROUND: The objective of this study was to adapt and improve previously published analysis methods aimed at the simultaneous determination of sulfonamide residues in edible animal tissues by capillary zone electrophoresis with electrochemical detection. RESULTS: The effects of several factors such as the acidity and concentration of running buffer, the separation voltage, the applied potential and the injection time on CZE‐ED were investigated. Complete separation of six sulfonamides was achieved within 17 min by using 40 mmol L^?1 Na₂B₄O₇/25 mmol L^?1 KH₂PO₄ (pH 6.2) at an applied voltage of 18 kV. Excellent linearity was obtained over two orders of magnitude with the improved detection limits (S/N = 3) ranged from 1.7 × 10^?7 to 4.4 × 10^?9 g mL^?1 for all six sulfonamides in comparison with previous reports. A solvent extraction/centrifuge/evaporation procedure was used to extract sulfonamides from animal tissues, sample clean‐up and pre‐concentration of sulfonamides prior to CZE‐ED analysis. Good recoveries from 81% to 92% were achieved. CONCLUSION: Results obtained in this work indicated that the proposed CZE‐ED method was sensitive, rapid and simple for the simultaneous determination of sulfonamides in edible animal tissues. Therefore, the new faster and easy handling procedure provides an additional powerful tool that can be employed for the analysis of sulfonamide residues in foodstuff. Copyright © 2009 Society of Chemical Industry     

Piperazine-based homo- and copolymers containing trivalent and quaternary nitrogen functionalities

The synthesis and solution properties of poly (1,1-diallyl-4-hydropiperazine dichloride) [poly(DAHPD)] ( 3 ), a dicationic polymer, and poly(1,1-diallylpiperazinium chloride), [poly(DAPC)] ( 4 ), a bifunctional polymer with trivalent and quaternary nitrogens, and their corresponding copolymers with sulfur dioxide, poly(DAHPD-SO₂) ( 6 ) and poly(DAPC-SO₂) ( 7 ), are discussed. Dicationic polymers ( 3 ) and ( 6 ) were found to have less pronounced polyelectrolyte effects than their monocationic counterparts ( 4 ) and ( 7 ). © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69:1329–1334, 1998     

胶体金免疫层析法检测食品中的磺胺类药物残留

建立了一种用于快速检测动物源性食品中五种磺胺类药物,磺胺异噁唑(SIZ)、磺胺噻唑(STZ)、磺胺对甲氧嘧啶(SME),磺胺甲二唑(SMT)、磺胺氯哒嗪(SCPA)残留的胶体金免疫层析方法.采用柠檬酸三钠还原法制备粒径为20nm的胶体金,将对磺胺类药物具有广谱特异性的多克隆抗体-肢体金复合物喷涂在玻璃纤维上,并将人工合...