Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,whic...Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.展开更多
Three chiral aminopyridine ligands derived from L-proline were prepared. Careful evaluation of the corresponding aminopyridine manganese complexes in asymmetric epoxidation of olefins revealed a broad substrate scope ...Three chiral aminopyridine ligands derived from L-proline were prepared. Careful evaluation of the corresponding aminopyridine manganese complexes in asymmetric epoxidation of olefins revealed a broad substrate scope in the presence of 0.2 mol% manganese complex and 0.5 equiv. 2,2-dimethylbutyric acid, with aqueous hydrogen peroxide as an oxidant. A variety of olefins including styrenes, chromenes, and cinnamamides were transformed successfully into the target epoxides with moderate to excellent enantioselectivity（yield up to 95%, ee up to 99%）.展开更多
Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral n...Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional recovery.We hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve injury.Mice with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP dose.While a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle controls.These findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal degeneration.The animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on March 31,2017.展开更多
A mixed complex [Zn（C5H6N2）（HL）2] （C5H6N2 = 2-aminopyridine, H2L = acetylacetone） has been synthesized and characterized by IR, elemental analysis and X-ray single-crystal diffraction analysis. The crystal belon...A mixed complex [Zn（C5H6N2）（HL）2] （C5H6N2 = 2-aminopyridine, H2L = acetylacetone） has been synthesized and characterized by IR, elemental analysis and X-ray single-crystal diffraction analysis. The crystal belongs to monoclinic, space group P21/c with a = 7.4490（15）, b = 8.2650（17）, c = 27.615（6） A°, β= 101.69（3）°, V = 1664.9（6）A°^3, Z = 4, Mr = 357.70, Dc = 1.427 g/cm^3, F（000） = 744, μ = 1.493 mm^-1, R = 0.0309 and wR = 0.0771. The Zn（Ⅱ） is coordinated by one nitrogen atom from 2-aminopyridine and four oxygen atoms from two acetylacetone anions to furnish a distorted square pyramid geometry. The complex forms a three-dimensional network through intermolecular hydrogen bonds.展开更多
Two diiron dithiolate complexes, （μ-pdt）Fe2（CO）5（C7H10N2） 3 and （μ-edt）-Fe2（CO）5（C7H10N2） 4 （pdt = -S（CH2）3S-, edt = -S（CH2）2S-）, have been synthesized and characterized by single-crystal X-ray dif...Two diiron dithiolate complexes, （μ-pdt）Fe2（CO）5（C7H10N2） 3 and （μ-edt）-Fe2（CO）5（C7H10N2） 4 （pdt = -S（CH2）3S-, edt = -S（CH2）2S-）, have been synthesized and characterized by single-crystal X-ray diffraction. Complex 3 crystallizes in the monoclinic system, space group P21/c with a = 10.168（4）, b = 11.816（4）, c = 16.595（7） and β = 95.195（6）o; and complex 4 crystallizes in the orthorhombic system, space group P212121 with a = 9.317（3）, b = 11.898（4）, c = 34.006（10） .The distances of Fe（1）–Fe（2） are 2.5058（9） in 3 and 2.4942（10） in 4, falling in the normal range of Fe–Fe bond length （2.49～2.57 ）. The cyclic voltammograms show that 3 and 4 display irreversible reduction peaks （FeIFeI/ FeIFe0） at –1.717 V and –1.673 V vs. Ag/AgCl, respectively. With different acids, complex 3 has distinguishable behavior, two protonations in addition of HBF4-Et2O and single protonation besides HOAc-CH3CN, and complex 4 has a similar action to 3 with HOAc-CH3CN for a semblable structure.展开更多
A chemoselective synthesis of novel indolizine derivatives were reported via three-component reactions of aminopyridines, acetylenic diesters and a-halo ketones. In these reactions, the zwitterion generated from amino...A chemoselective synthesis of novel indolizine derivatives were reported via three-component reactions of aminopyridines, acetylenic diesters and a-halo ketones. In these reactions, the zwitterion generated from aminopyridines and acetylenic diesters reacted with a-halo ketones to produce indolizine skeleton in good to high yields under mild reaction conditions.展开更多
Reaction of zinc acetate, potassium thiocyanate and the ligand 3-ampy gave the discrete tetrahedral complex [Zn(NCS)<sub>2</sub>(3-ampy)<sub>2</sub>] in which 3-ampy chelates in a monodentate f...Reaction of zinc acetate, potassium thiocyanate and the ligand 3-ampy gave the discrete tetrahedral complex [Zn(NCS)<sub>2</sub>(3-ampy)<sub>2</sub>] in which 3-ampy chelates in a monodentate fashion through its pyridine-N atom. It was characterized by single crystal X-ray diffraction, infrared, and elemental analysis. Density Functional Theory calculations were performed in order to gain insights into the role of weak molecular interactions in the complex that influence the self-assembly process and crystal packing. X---H (X = H, C, N and S) inter-actions. S-H interactions (30.2%) were found to be the main interactions that hold the molecules in the crystal structure. Furthermore, the thermolysis of the complex was studied in order to evaluate whether it was suitable as a precursor for zinc sulphide.展开更多
A three-dimensional complex [Cu（3-ampy）（HEO）4]（SO4）·（H2O） （3-ampy = 3-amino- pyridine） has been synthesized. Crystallographic data： C5H16CuN2O9S, Mr = 343.80, triclinic, space group P1, a = 7.675（2）,...A three-dimensional complex [Cu（3-ampy）（HEO）4]（SO4）·（H2O） （3-ampy = 3-amino- pyridine） has been synthesized. Crystallographic data： C5H16CuN2O9S, Mr = 343.80, triclinic, space group P1, a = 7.675（2）, b = 8.225（3）, c = 10.845（3）A, α= 86.996（4）, β = 76.292（4）, γ= 68.890（4）°, V = 620.0（3）A^3, Z = 2, Dc = 1.841 g/cm^3, F（000） = 354 and μ = 1.971 mm^-1. The structure was refined to R = 0.0269 and wR = 0.0659 for 1838 observed reflections （I 〉 2a（/））. The structure consists of [Cu（3-ampy）（H2O）4]^2＋ cations, SO4^2- anions and lattice water molecules. 3-Ampy acting as a bidentate bridging ligand generates a 1D covalent chain. A supramolecular 2D framework is formed through π-π stacking of pyridine rings. The lattice water molecules and SO4^2- anions are located between the adjacent 2D frameworks. The hydrogen bonding interactions from lattice water molecules and SO4^2- anions to coordinate water extend the 2D framework into a 3D network.展开更多
Seven transition metal complexes of Mn<sup>2+</sup>, Ni<sup>2+</sup>, Co<sup>2+</sup>, Cu<sup>2+</sup> and Zn<sup>2+</sup> with 3-aminopyridine (3-APy) as li...Seven transition metal complexes of Mn<sup>2+</sup>, Ni<sup>2+</sup>, Co<sup>2+</sup>, Cu<sup>2+</sup> and Zn<sup>2+</sup> with 3-aminopyridine (3-APy) as ligand have been synthesized, characterized by different techniques and their antibacterial activities were studied. Molecular modeling calculations were performed using DMOL<sup>3</sup> program in materials studio package which is designed for the realization of large scale density functional theory calculation (DFT). The quantum mechanical and chemical reactivity parameters such as chemical hardness, chemical potential, electronegativity, electrophilicity index and Homo-Lumo energy gap were obtained theoretically and were used to understand the biological activity of the prepared compounds. Some complexes were tested for their in-vitro cytotoxic activity in human lung cancer cell lines (A-549 cell line), and structureactivity relationships were established. In general, the coordination to Co<sup>2+</sup> increased the cytotoxicity while the Ni<sup>2+</sup> complexes show reduced cytotoxic activity compared to the metal-free 3-aminopyridine.展开更多
目的:借鉴美国的临床药师培养模式,完善我国药学专业型人才培养方法,培养出能指导临床合理用药的临床药师。方法:以美国南加州大学药学院(USC school of pharmacy)的Pharm D教育为例,简单介绍美国如何培养Pharm D的临床实践能力,并与我...目的:借鉴美国的临床药师培养模式,完善我国药学专业型人才培养方法,培养出能指导临床合理用药的临床药师。方法:以美国南加州大学药学院(USC school of pharmacy)的Pharm D教育为例,简单介绍美国如何培养Pharm D的临床实践能力,并与我国现行的临床药师培养模式进行对比。结果:我国药学院课程设置不够合理,本科毕业生缺乏临床思维,无法胜任临床药师一职。结论:从课程、学制、毕业后教育等方面入手,改良传统药学教育模式,培养具备丰富临床实践经验的药学人才。展开更多
以美国内布拉斯加医学中心(University of Nebraska Medical Center,UNMC)岗位胜任力为导向培养Pharm.D.为例,介绍了其灵活多样的课堂教学方法、丰富充实的实践课程、注重人文素质培养的教育理念。临床中药学作为一门新兴的医药交叉学科...以美国内布拉斯加医学中心(University of Nebraska Medical Center,UNMC)岗位胜任力为导向培养Pharm.D.为例,介绍了其灵活多样的课堂教学方法、丰富充实的实践课程、注重人文素质培养的教育理念。临床中药学作为一门新兴的医药交叉学科,对人才的培养存在一些不足,建议结合美国Pharm.D.培养的先进经验,构建符合学科特色的临床中药学人才培养体系,培养优秀的临床中药学人才,为中医药事业的持续发展做出贡献。展开更多
In order to carry out the comprehensive reform of the professional master’s degree training mode of clinical pharmacy, we carried out interviews among 91 persons on the professional master’s degree of clinical pharm...In order to carry out the comprehensive reform of the professional master’s degree training mode of clinical pharmacy, we carried out interviews among 91 persons on the professional master’s degree of clinical pharmacy in Peking University School of Pharmaceutical Sciences and collected extensive feedback. We preliminaries explore the mode of Doctor of Pharmacy（Pharm. D.） Education, laying the foundation for Doctor’s education of professional clinical pharmacy in China. We conducted investigations and interviews among 91 clinical pharmacists and students of Peking University School of Pharmaceutical Sciences on the training of professional master’s degree and Pharm. D. education mode, which includes 67 postgraduates and 24 clinical pharmacists. Respondents put forward the problems of training mode and corresponding suggestions and opinions from different aspects during the investigation and interview. The results mainly divide into four aspects： curriculum setting, clinical practice, assessme nt system and teaching resources. Respondents put forward effective feedback on the above four aspects, which are beneficial to the comprehensive reform of the training mode of professional master degree in clinical pharmacy and preliminary exploration of Pharm. D. Education in China.展开更多
文摘Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.
基金supported by the National Natural Science Foundation of China(21473226,21773273)Key Research Program of Frontier Sciences,CAS(QYZDJ-SSW-SLH051)Natural Science Foundation of Jiangsu Province(BK20170420)~~
文摘Three chiral aminopyridine ligands derived from L-proline were prepared. Careful evaluation of the corresponding aminopyridine manganese complexes in asymmetric epoxidation of olefins revealed a broad substrate scope in the presence of 0.2 mol% manganese complex and 0.5 equiv. 2,2-dimethylbutyric acid, with aqueous hydrogen peroxide as an oxidant. A variety of olefins including styrenes, chromenes, and cinnamamides were transformed successfully into the target epoxides with moderate to excellent enantioselectivity（yield up to 95%, ee up to 99%）.
基金supported by grants from the National Institutes of Health(K08 AR060164-01A)Department of Defense(W81XWH-16-1-0725)to JCE in addition to institutional support from the University of Rochester and Pennsylvania State University Medical Centers
文摘Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional recovery.We hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve injury.Mice with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP dose.While a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle controls.These findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal degeneration.The animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on March 31,2017.
基金This work was supported by Qingdao Science and Technology Plan Items (03-3-nsh-28)
文摘A mixed complex [Zn（C5H6N2）（HL）2] （C5H6N2 = 2-aminopyridine, H2L = acetylacetone） has been synthesized and characterized by IR, elemental analysis and X-ray single-crystal diffraction analysis. The crystal belongs to monoclinic, space group P21/c with a = 7.4490（15）, b = 8.2650（17）, c = 27.615（6） A°, β= 101.69（3）°, V = 1664.9（6）A°^3, Z = 4, Mr = 357.70, Dc = 1.427 g/cm^3, F（000） = 744, μ = 1.493 mm^-1, R = 0.0309 and wR = 0.0771. The Zn（Ⅱ） is coordinated by one nitrogen atom from 2-aminopyridine and four oxygen atoms from two acetylacetone anions to furnish a distorted square pyramid geometry. The complex forms a three-dimensional network through intermolecular hydrogen bonds.
基金Supported by the National Natural Science Foundation of China (No. 20973172, 21071145)the National Basic Research Program of China (No. 2009CB220009)
文摘Two diiron dithiolate complexes, （μ-pdt）Fe2（CO）5（C7H10N2） 3 and （μ-edt）-Fe2（CO）5（C7H10N2） 4 （pdt = -S（CH2）3S-, edt = -S（CH2）2S-）, have been synthesized and characterized by single-crystal X-ray diffraction. Complex 3 crystallizes in the monoclinic system, space group P21/c with a = 10.168（4）, b = 11.816（4）, c = 16.595（7） and β = 95.195（6）o; and complex 4 crystallizes in the orthorhombic system, space group P212121 with a = 9.317（3）, b = 11.898（4）, c = 34.006（10） .The distances of Fe（1）–Fe（2） are 2.5058（9） in 3 and 2.4942（10） in 4, falling in the normal range of Fe–Fe bond length （2.49～2.57 ）. The cyclic voltammograms show that 3 and 4 display irreversible reduction peaks （FeIFeI/ FeIFe0） at –1.717 V and –1.673 V vs. Ag/AgCl, respectively. With different acids, complex 3 has distinguishable behavior, two protonations in addition of HBF4-Et2O and single protonation besides HOAc-CH3CN, and complex 4 has a similar action to 3 with HOAc-CH3CN for a semblable structure.
基金supported by the Research Council of the University of Mazandaran,Iran
文摘A chemoselective synthesis of novel indolizine derivatives were reported via three-component reactions of aminopyridines, acetylenic diesters and a-halo ketones. In these reactions, the zwitterion generated from aminopyridines and acetylenic diesters reacted with a-halo ketones to produce indolizine skeleton in good to high yields under mild reaction conditions.
文摘Reaction of zinc acetate, potassium thiocyanate and the ligand 3-ampy gave the discrete tetrahedral complex [Zn(NCS)<sub>2</sub>(3-ampy)<sub>2</sub>] in which 3-ampy chelates in a monodentate fashion through its pyridine-N atom. It was characterized by single crystal X-ray diffraction, infrared, and elemental analysis. Density Functional Theory calculations were performed in order to gain insights into the role of weak molecular interactions in the complex that influence the self-assembly process and crystal packing. X---H (X = H, C, N and S) inter-actions. S-H interactions (30.2%) were found to be the main interactions that hold the molecules in the crystal structure. Furthermore, the thermolysis of the complex was studied in order to evaluate whether it was suitable as a precursor for zinc sulphide.
基金the Natural Science Found Council of China (Nos. 20671011, 20331010, 90406002 and 90406024) the Key Laboratory of Structural Chemistry Foundation (No. 060017)
文摘A three-dimensional complex [Cu（3-ampy）（HEO）4]（SO4）·（H2O） （3-ampy = 3-amino- pyridine） has been synthesized. Crystallographic data： C5H16CuN2O9S, Mr = 343.80, triclinic, space group P1, a = 7.675（2）, b = 8.225（3）, c = 10.845（3）A, α= 86.996（4）, β = 76.292（4）, γ= 68.890（4）°, V = 620.0（3）A^3, Z = 2, Dc = 1.841 g/cm^3, F（000） = 354 and μ = 1.971 mm^-1. The structure was refined to R = 0.0269 and wR = 0.0659 for 1838 observed reflections （I 〉 2a（/））. The structure consists of [Cu（3-ampy）（H2O）4]^2＋ cations, SO4^2- anions and lattice water molecules. 3-Ampy acting as a bidentate bridging ligand generates a 1D covalent chain. A supramolecular 2D framework is formed through π-π stacking of pyridine rings. The lattice water molecules and SO4^2- anions are located between the adjacent 2D frameworks. The hydrogen bonding interactions from lattice water molecules and SO4^2- anions to coordinate water extend the 2D framework into a 3D network.
文摘Seven transition metal complexes of Mn<sup>2+</sup>, Ni<sup>2+</sup>, Co<sup>2+</sup>, Cu<sup>2+</sup> and Zn<sup>2+</sup> with 3-aminopyridine (3-APy) as ligand have been synthesized, characterized by different techniques and their antibacterial activities were studied. Molecular modeling calculations were performed using DMOL<sup>3</sup> program in materials studio package which is designed for the realization of large scale density functional theory calculation (DFT). The quantum mechanical and chemical reactivity parameters such as chemical hardness, chemical potential, electronegativity, electrophilicity index and Homo-Lumo energy gap were obtained theoretically and were used to understand the biological activity of the prepared compounds. Some complexes were tested for their in-vitro cytotoxic activity in human lung cancer cell lines (A-549 cell line), and structureactivity relationships were established. In general, the coordination to Co<sup>2+</sup> increased the cytotoxicity while the Ni<sup>2+</sup> complexes show reduced cytotoxic activity compared to the metal-free 3-aminopyridine.
文摘目的:借鉴美国的临床药师培养模式,完善我国药学专业型人才培养方法,培养出能指导临床合理用药的临床药师。方法:以美国南加州大学药学院(USC school of pharmacy)的Pharm D教育为例,简单介绍美国如何培养Pharm D的临床实践能力,并与我国现行的临床药师培养模式进行对比。结果:我国药学院课程设置不够合理,本科毕业生缺乏临床思维,无法胜任临床药师一职。结论:从课程、学制、毕业后教育等方面入手,改良传统药学教育模式,培养具备丰富临床实践经验的药学人才。
文摘以美国内布拉斯加医学中心(University of Nebraska Medical Center,UNMC)岗位胜任力为导向培养Pharm.D.为例,介绍了其灵活多样的课堂教学方法、丰富充实的实践课程、注重人文素质培养的教育理念。临床中药学作为一门新兴的医药交叉学科,对人才的培养存在一些不足,建议结合美国Pharm.D.培养的先进经验,构建符合学科特色的临床中药学人才培养体系,培养优秀的临床中药学人才,为中医药事业的持续发展做出贡献。
文摘In order to carry out the comprehensive reform of the professional master’s degree training mode of clinical pharmacy, we carried out interviews among 91 persons on the professional master’s degree of clinical pharmacy in Peking University School of Pharmaceutical Sciences and collected extensive feedback. We preliminaries explore the mode of Doctor of Pharmacy（Pharm. D.） Education, laying the foundation for Doctor’s education of professional clinical pharmacy in China. We conducted investigations and interviews among 91 clinical pharmacists and students of Peking University School of Pharmaceutical Sciences on the training of professional master’s degree and Pharm. D. education mode, which includes 67 postgraduates and 24 clinical pharmacists. Respondents put forward the problems of training mode and corresponding suggestions and opinions from different aspects during the investigation and interview. The results mainly divide into four aspects： curriculum setting, clinical practice, assessme nt system and teaching resources. Respondents put forward effective feedback on the above four aspects, which are beneficial to the comprehensive reform of the training mode of professional master degree in clinical pharmacy and preliminary exploration of Pharm. D. Education in China.
