左旋氧氟沙星不对称合成新方法研究

以(S)-乳酸乙酯为手性起始原料,经10步反应合成了抗菌药物左旋氧氟沙星。该方法起始原料丰富易得,反应条件温和,收率好,产物光学纯度高。     

抗病毒药物研究新进展

抗病毒药物研究新进展胡增建，蒋华良，杨玉社，陈凯先，嵇汝运（中国科学院上海药物研究所，上海２０００３１）中国图书分类号Ｒ９７８．７病毒感染的疾病种类繁多，危害很大，但抗病毒药物的发展却十分缓慢，这主要是由于病毒的结构和生物过程简单，不易与宿主细胞加以...     

疼痛的处理措施及其生理学基础

七十年代以来,对疼痛理论研究使人们对疼痛产生的机理和疼痛的调制有了许多新的认识,这对一些减轻疼痛的新方法的应用发挥了积极的作用。本文综述了临床上采用的疼痛处理措施及有关药物镇痛的一些新的给药方式,并指出了其生理学基础,以有助于护士帮助他们的病人战胜疼痛。     

Molecular modeling of voltage-gated potassium channel pore

目的：建立和验证电压门控型钾通道的结构模型．方法：（１）从实验和理论研究结果中提取结构约束条件；（２）建立满足这些约束条件的初始结构模型，并进一步用限制性分子力学优化；（３）根据模型能否成功地解释通道功能分子机制和许多实验事实来判断其合理性．结果：（１）建立了一个孔区模型，其中信号序列残基（对应Ｓｈａｋｅｒ４３９－４４６）以非周期性构象嵌入膜中并形成孔区比较窄的部分，而孔区域的其它残基构成孔区外口；（２）通道离子选择性在４４５，４４７位置处分别通过阳离子π轨道作用机理和氧笼机理来实现；（３）ＣＴＸ和ＡｇＴｘ２与孔区的不同结合方式导致了它们通道亲和力的差异；（４）孔区内侧静电势主要为负．结论：构建的模型与从实验结果导出的限制信息是相一致的．     

Analysis of electronic structures of physostigmine analogs

ＡｎａｌｙｓｉｓｏｆｅｌｅｃｔｒｏｎｉｃｓｔｒｕｃｔｕｒｅｓｏｆｐｈｙｓｏｓｔｉｇｍｉｎｅａｎａｌｏｇｓＨＵＺｅｎｇＪｉａｎ，ＪＩＡＮＧＨｕａＬｉａｎｇ，ＣＨＥＮＪｉａｎＺｈｏｎｇ，ＣＨＥＮＫａｉＸｉａｎ１，ＪＩＲｕＹｕｎ（Ｓｈａｎｇｈａｉ...     

毒扁豆碱类似物电子结构分析

AIM: To elucidate the action mechanism and structural prerequisites of 21 physostigmine analogs as acetylcholinesterase inhibitors at the molecular level, and help the rational design of these dihydroindoline inhibitors. METHODS: Initial structures of these compounds were built and minimized by SYBYL 6.2 molecular modeling software. Conformations of those molecules with the highest predictive abilities in the Comparative Molecular Field Analysis model were chosen to the semiempirical quantum chemical calculations. RESULTS: (1) The highest occupied molecular orbital (HOMO) consisted mainly of the orbitals in phenyl group and N1 atom; the lowest unoccupied molecular orbital (LUMO) of the molecules was contributed from phenyl group and C11 atom. While the HOMO energies did not show any recognizable relationship with activity, the LUMO energies showed a decreased tendency with increasing activity. The active compounds showed lower LUMO energies. (2) The carbon atom (C11) had the most positive net atom charge. The most active compound had the most positive charge on this carbon, but had the lower charges on the carbonyl oxygen (O12) which was the most negative charge atom. (3) The bond order of carbon-oxygen bond (C11-O10) was invariant across the series of the compounds. (4) Compounds with too high or too low total dipole moment had lower activities, while the most active one had a lower molecular polarizability. CONCLUSION: A molecular model was suggested to explain the possible mode of action by which these compounds inhibit acetylcholinesterase.     

量子药理学计算方法的现状和展望

引言量子药理学是当代药理学的一个重要组成部分,是在药理学经验知识的基础上,运用量子化学的原理和方法研究药物作用机制及其规律的一门基础理论学科。量子药理学的诞生,标志着当代药理学的研究正在由定性向定量、从宏观到微观、从形态到结构、从实验到理论转变,药物作用机制的研究已由最初的系统、器官水平逐步深入到细胞、亚细胞、分子和电子水平。     

左旋氧氟沙星类似物的合成及其构效关系

目的：发现新型高效的喹诺酮类抗菌药。方法和结果：设计合成了23个左旋氧氟沙星类似物,其中化合物5～23为新化合物,测定了它们对5株革兰阳性菌和5株革兰阴性菌的体外抗菌活性(MIC),并讨论了构效关系。结论：8-位氨基有利于提高喹诺酮抗阳性菌活性,化合物13,14的抗菌活性优于对照样品左旋氧氟沙星及环丙沙星。