新型磺酰类醛糖还原酶抑制剂的合成及活性研究

以2,4-二甲苯胺为原料,设计并合成了一系列环外磺酰胺(酯)类衍生物,对目标化合物的醛糖还原酶(ALR2)抑制活性进行了测定,并利用分子对接方法研究了抑制剂与醛糖还原酶蛋白的结合模式. 结果显示环外磺酰类化合物8a-d, 12a-b, 16a-b具有良好的体外醛糖还原酶抑制活性,分子模拟预测其能与酶蛋白的活性位点空腔较好结合. 化合物8a-d是一类新型醛糖还原酶抑制剂,活性良好,并可作为先导化合物探索活性更高的醛糖还原酶抑制剂.      

一个多用途吡咯烷类氮杂糖中间体的不对称合成

报道了多用途的吡咯烷类氮杂糖中间体6的不对称合成.起始原料(2R,3R,4S)-2-苄氧甲基-3,4-二苄氧基-5-氧代吡咯烷-1-羧酸叔丁酯(8)由手性合成砌块酒石酸酰亚胺7按照先前本实验室报道的方法经4步得到.活化的酰胺8经乙烯基加成、立体选择性还原、环化、氧化断裂双键成醛以及还原醛成醇等步骤得到了氮杂糖中间体(2R,3R,4R,5R)-2-羟甲基-3,4-二苄氧基-5-苄氧甲基吡咯烷-1-羧酸叔丁酯(6).从活化的酰胺8出发,经过5步反应,立体选择性地合成了氮杂糖中间体6,总产率46%.中间体6可用于多个吡咯烷类氮杂糖的合成.     

取向电工钢加工过程中第二相粒子的析出行为

利用场发射扫描电镜观察了以MnS为主要抑制剂的普通取向电工钢加工过程中第二相粒子的分布状态,统计了粒子面密度、平均尺寸以及相应的尺寸分布.结果显示,热轧加工造成了大量第二相粒子弥散、细小地析出,同时基体仍保持过饱和状态.冷轧变形会造成第二相粒子的回溶行为,而基体的过饱和状态会减弱回溶现象.中间退火与脱碳退火过程中会同时存在新粒子的形核及已析出粒子的粗化两个过程,而在最终二次再结晶升温阶段则以第二相粒子明显粗化为主.     

苯甲酰基脲类几丁质生物合成抑制剂的研究进展

对苯甲酰基脲类几丁质生物合成抑制剂结构组成的三个基本骨架：苯甲酰基，脲桥及苯基的修构效关系的研究进展情况进行了综述，并对该领域的研究前景进行了展望。     

1-羟基苯并三氮唑和钼酸钠对铜的缓蚀协同作用

采用电化学、扫描电子显微镜、X射线光电子能谱等实验方法研究了1-羟基苯并三氮唑(BTAOH)和钼酸钠(Na2Mo O4)复配后对铜在ASTM D 1384模拟大气腐蚀溶液中的缓蚀协同作用.电化学实验结果表明:BTAOH与Na2Mo O4在50 mg·L-1的质量浓度条件下,以2∶1复配使用能够显著提高铜在模拟大气腐蚀溶液中的电荷转移电阻,降低腐蚀电流密度,缓蚀率达到90.7%;铜在模拟大气腐蚀溶液中的腐蚀产物呈聚集柱状堆砌在表面,而在含有缓蚀剂的溶液中表面平整致密,且疏水性增强,接触角显著增大至91.8°.X射线光电子能谱结果显示Na2Mo O4与铜表面作用后形成Mo O3和Mo O2,两种氧化物填充在BTAOH形成的表面膜的缝隙中,提高了膜的致密性,对铜产生良好的保护作用.     

α,β-不饱和酰胺TRPV1抑制剂的Topomer CoMFA模型

利用SYBYL软件中的Topomer CoMFA方法分析了α,β-不饱和酰胺类TRPV1抑制剂的三维定量构效关系(3D-QSAR)模型.分子被分开为羰基和氨基两个基团,在Topomer CoMFA模型考察了立体场和静电场对抑制活性的影响.结果显示:去一交叉验证的相关系数q2为0.702,模型的预测相关系数r2为0.881.说明所建立的模型在统计上有较好的稳定性和预测能力,有助于TRPV1抑制剂的研发.     

Esterases of the flounder (Platichthys flesus,Pleuronectidae, Teleostei): Development of an identification protocol using starch gel electrophoresis and characterization of loci

Summary Fish esterases are among the most difficult enzymes to identify using starch gel electrophoresis because of the many loci that are simultaneously active, and especially because of duplication phenomena, satellite bands, and stain trails. In an attempt to simplify and clarify electropherograms, various staining and inhibitory methods were tested on esterases from the flounderPlatichthys flesus. A range of migration and staining buffers and substrates were used, as well as chemical inhibition and heat inactivation. A combination of the methods made it possible to distinguish and characterize the five presumed esterase loci.     

Introduction: integrins, dynamic cell receptors

Integrins are a family of adhesive receptors consisting of α- and β-subunits which attach cells together via adhesive protein ligands or bind cells to extracellular matrix. They are found on virtually all cell types and link the external ligand to the cytoskeleton of the cell. Integrins also act as signal transducers both from the outside of the cell to the interior and also inside-out. Their main functions are in recognition and in tight but regulated binding. The series of reviews presented here cover both basic aspects of integrin function, including signal transduction, snake disintegrins and structure and function of I-domains in some integrin α-subunits, as well as the role of integrins in diseases, cancer, inflammation and cardiovascular diseases. The search for suitable inhibitors of integrins for treatment of these diseases and future prospects for their use are also discussed.     

Integrins and cardiovascular disease

Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus, blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen receptor α _IIb  β ₃ , has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence and mortality due to these disorders. The development of α _IIb  β ₃ inhibitors is an important strategy of many pharmaceutical companies which foresee a large market for the treatment of acute conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prophylaxis of these conditions. Although all the associated problems have not been solved, the undoubted improvements in patient care resulting from the first of these treatments in the clinic have stimulated further research on the role of integrins on other vascular cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with specific integrin subunit genes ablated have contributed to a better understanding of the function of integrins in development of the cardiovascular system.     

新型低膦系列水质稳定剂--膦酸基羟乙酸的研究

以二烷基亚磷酸酯与乙醛酸为原料,经一步反应得到膦酸基羟乙酸(HPA),产率为70%. 采用红外光谱、31P-NMR及液相色谱分析证实了合成产物的分子结构. 此合成路线克服了欧洲专利报道的剧毒、苛刻的反应条件和复杂的工艺路线等缺点. 对HPA的耐蚀性进行了探讨,得到了理想的结果.