A series of ethyl 5-hydroxyindole-3-earboxylates 6a-10r was designed and synthesized. The structures of all the compounds were confirmed by IR, ^1H NMR, and MS and their anti-hepatitis B virus （HBV） activities were ...A series of ethyl 5-hydroxyindole-3-earboxylates 6a-10r was designed and synthesized. The structures of all the compounds were confirmed by IR, ^1H NMR, and MS and their anti-hepatitis B virus （HBV） activities were evaluated in 2.2.15 cells. Among them, compound 7g { ethyl 5-hydroxy-2- [ （ 3-methoxyphenylsulfinyl ） methyl ] -1-methyl-4- [ （4-methylpiperazin-1-yl） methyl ]-1H-indole-3-carboxylate} displays a significant anti-HBV activity, which is more potent than the positive control lamivudine.展开更多
The title compound （ethyl5-（4-（2-phenylacetamido）phenyl）-lH-pyrazole-3-carboxylate, C20H19N3O3） was synthesized by the reaction of Claisen condensation, cyclization, reduction and acylation. The structure was ch...The title compound （ethyl5-（4-（2-phenylacetamido）phenyl）-lH-pyrazole-3-carboxylate, C20H19N3O3） was synthesized by the reaction of Claisen condensation, cyclization, reduction and acylation. The structure was characterized by X-ray diffraction, MS, NMR and IR. It belongs to the monoclinic system, space group C2/c with a = 22.723（9）, b = 9.324（4）, c = 18.890（8） A, β = 114.259（6）°, V = 3649（3） A^3, Dc = 1.272 Mg·m^3, Z = 8, Mr = 349.38, p = 0.087 mm^-1, F（000） = 1472, the final R = 0.0615 and wR = 0.1643. The biological test shows that the title compound has a moderate acrosin inhibition activity.展开更多
The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined...The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.展开更多
Five coordination compounds, namely [Ni2(5-Fnic)2(H2 O)4](1), [Ni(5-Fnic)(μ-5-Fnic)(H2 biim)]n(2), {[Cd((μ-5-Fnic)2(H2 O)2]×4,4’-bipy}n(3), [Pb2(μ-5-Fnic)2(μ3-5-Fnic)2(H2 O)2]n(4), and [Pb(5-Fnic)2(4,4’-bip...Five coordination compounds, namely [Ni2(5-Fnic)2(H2 O)4](1), [Ni(5-Fnic)(μ-5-Fnic)(H2 biim)]n(2), {[Cd((μ-5-Fnic)2(H2 O)2]×4,4’-bipy}n(3), [Pb2(μ-5-Fnic)2(μ3-5-Fnic)2(H2 O)2]n(4), and [Pb(5-Fnic)2(4,4’-bipy)(H2 O)](5), have been constructed hydrothermally using 5-FnicH(5-FnicH = 5-fluoronicotinic acid), H2 biim(H2 biim = 2,2’-biimidazole), 4,4’-bipy(4,4’-bipy = 4,4’-bipyridine), NiCl2×6 H2 O, CdCl2×H2 O and PbCl2. The products were isolated as stable crystalline solids and were characterized by IR spectra, elemental analyses, thermogravimetric analyses(TGA), and single-crystal X-ray diffraction analyses. Structures of 1~5 range from discrete 0 D monomers(1 and 5) to 1 D coordination polymers(2 and 4) and 2 D metal-organic network(3). A broad structural diversity of 1~5 is guided by the type of the metal(Ⅱ) node and the introduction of auxiliary ligands. The magnetic(for 2) and luminescent(for 3~5) properties were also investigated and discussed.展开更多
Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibito...Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.展开更多
The reaction of Mn(OAc)2·4 H2 O, 5-ethyl-pyridine-2,3-dicarboxylic acid(H2 epda) and 4,4?-bipyridine(4,4?-bipy)/4,4?-bis(imidazolyl)biphenyl)(bibp) under hydrothermal conditions produced two new manganese(Ⅱ) MOF...The reaction of Mn(OAc)2·4 H2 O, 5-ethyl-pyridine-2,3-dicarboxylic acid(H2 epda) and 4,4?-bipyridine(4,4?-bipy)/4,4?-bis(imidazolyl)biphenyl)(bibp) under hydrothermal conditions produced two new manganese(Ⅱ) MOFs [Mn(epda)(4,4?-bipy)1/2](1) and [Mn(epda)(bibp)1/2](2), which were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analyses, and single-crystal X-ray diffraction. The structures of complexes 1 and 2 are similar. In 1, the adjacent Mn(Ⅱ) ions are connected by epda dianion to generate a 2 D(4,4) grid layer, and such 2 D layers are further connected via bibp ligand to form another layer, forming a 2 D pillared-layer. Topologically, the Mn atoms as the node are bridged by the edpa anions and bibp ligands to form a uninodal 5-connected network topology. The magnetic properties of 1 and 2 have also been-investigated, and the exchange interctions were –1.39 and –1.05 cm1, respectively. According to the crystal structures, compounds 1 and 2 were carried out by using hybrid DFT methods at the B3 LYP/6-31 G(d) level. The DFT-BS approach was applied to study the magnetic coupling behaviors for 1 and 2. The result reveals that the calculated exchange coupling constants J were in good agreement with the experimental data.展开更多
A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.
Methyl 3-（5-bromo-l-ethyl-lH-indole-3-carbonyl）aminopropionate has been synthesized by the acylation of 5-bromo-3-trichloroacetylindole with β-alanine methyl ester, followed by alkylation with ethyl iodide, in 82.6...Methyl 3-（5-bromo-l-ethyl-lH-indole-3-carbonyl）aminopropionate has been synthesized by the acylation of 5-bromo-3-trichloroacetylindole with β-alanine methyl ester, followed by alkylation with ethyl iodide, in 82.6% yield. Its crystal structure was gotten and determined by X-ray diffraction method. The crystal is of monoclinic, space group P2/c with a = 11.7927（8）, b = 14.9342（8）, c = 9.0060（5） A, β = 101.558（6）°, V = 1553.93（16） A3, Z = 4, Dc= 1.510 g/cm3, 2 = 0.71073 A,μ（MoKa） = 2.656 mm-1, Mr = 353.22 and F（000） = 720. The structure was refined to R = 0.0401 and wR = 0.0825 for 1704 observed reflections with I 〉 2σ（I）. In the crystal structure, intermolecular N（2）-H（2）...O（1） hydrogen bond and weak intermolecular bonds （C（1）-H（1）...O（1） and C（10）-H（10B）-O（2）） are formed, and π-π stacking also exists.展开更多
Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous ant...Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous anti-TNF-α agents have been developed to reduce its circulating levels either by neutralizing, binding or inhibiting the de novo synthesis with the aim of achieving desirable therapeutic effects. In the present study, we compared the effects of a protein-based anti-TNF-α drug, etanercept, and a non-protein-based anti-TNF-α small molecule, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), on the LPS-stimulated secretion of TNF-α in the medium and TNF-α associated with the THP-1 cells in vitro. Both drugs had marked concentration-dependent inhibitory effects on the LPS-stimulated secretion of TNF-α. However, their effects on the LPS-stimulated cell-associated TNF-α were diametrically opposed to each other. For instance, etanercept further increased the level by up to 12-fold, whereas 5-EPP inhibited the level in a dose dependent manner. In addition, 5-EPP caused a significant reduction in the elevated level of cell associated TNF-α caused by LPS + etanercept. The differences in the levels of cell-associated TNF-α as reported in the present study may partly explain the adverse effects of some protein-based anti-TNF-α drugs including etanercept as opposed to a non-protein-based anti-TNF-α drug such as pirfenidone, a structural analogue of 5-EPP, for treatment of some TNF-α mediated diseases. It was concluded from the findings of this study that drugs which elevate the levels of cell associated-TNF-α will potentially have more adverse events even after reducing the secreted levels of TNF-α than the drugs which reduce both the secreted and cell-associated TNF-α levels.展开更多
基金Supported by the National Natural Science Foundation of China(No.20042047).
文摘A series of ethyl 5-hydroxyindole-3-earboxylates 6a-10r was designed and synthesized. The structures of all the compounds were confirmed by IR, ^1H NMR, and MS and their anti-hepatitis B virus （HBV） activities were evaluated in 2.2.15 cells. Among them, compound 7g { ethyl 5-hydroxy-2- [ （ 3-methoxyphenylsulfinyl ） methyl ] -1-methyl-4- [ （4-methylpiperazin-1-yl） methyl ]-1H-indole-3-carboxylate} displays a significant anti-HBV activity, which is more potent than the positive control lamivudine.
基金supported by the Science and technology support program of Jiangsu Province (2010, BE2010682)
文摘The title compound （ethyl5-（4-（2-phenylacetamido）phenyl）-lH-pyrazole-3-carboxylate, C20H19N3O3） was synthesized by the reaction of Claisen condensation, cyclization, reduction and acylation. The structure was characterized by X-ray diffraction, MS, NMR and IR. It belongs to the monoclinic system, space group C2/c with a = 22.723（9）, b = 9.324（4）, c = 18.890（8） A, β = 114.259（6）°, V = 3649（3） A^3, Dc = 1.272 Mg·m^3, Z = 8, Mr = 349.38, p = 0.087 mm^-1, F（000） = 1472, the final R = 0.0615 and wR = 0.1643. The biological test shows that the title compound has a moderate acrosin inhibition activity.
基金supported by the Natural Science Foundation of Hubei Province (2006ABB016)Key Science Research Project of Hubei Provincial Department of Education (No.D200724001) the Science Research Project of Yunyang Medical College (No. 2006QDJ16)
文摘The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.
基金supported by Guangdong Province Higher Vocational Colleges&Schools Pearl River Scholar Funded Scheme(2015,2018)the Natural Science Foundation of Guangdong Province(No.2016A030313761)+3 种基金the Pearl River Scholar Foundation of Guangdong Industry Polytechnic(RC2015-001)the Opening Foundation of MOE Key Laboratory of MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University(2016)Innovation Team Project on University of Guangdong Province(2017GKCXTD001,2017GWCXTD002)Outstanding youth fund project of Guangdong Industry Polytechnic(QN 2018-007)
文摘Five coordination compounds, namely [Ni2(5-Fnic)2(H2 O)4](1), [Ni(5-Fnic)(μ-5-Fnic)(H2 biim)]n(2), {[Cd((μ-5-Fnic)2(H2 O)2]×4,4’-bipy}n(3), [Pb2(μ-5-Fnic)2(μ3-5-Fnic)2(H2 O)2]n(4), and [Pb(5-Fnic)2(4,4’-bipy)(H2 O)](5), have been constructed hydrothermally using 5-FnicH(5-FnicH = 5-fluoronicotinic acid), H2 biim(H2 biim = 2,2’-biimidazole), 4,4’-bipy(4,4’-bipy = 4,4’-bipyridine), NiCl2×6 H2 O, CdCl2×H2 O and PbCl2. The products were isolated as stable crystalline solids and were characterized by IR spectra, elemental analyses, thermogravimetric analyses(TGA), and single-crystal X-ray diffraction analyses. Structures of 1~5 range from discrete 0 D monomers(1 and 5) to 1 D coordination polymers(2 and 4) and 2 D metal-organic network(3). A broad structural diversity of 1~5 is guided by the type of the metal(Ⅱ) node and the introduction of auxiliary ligands. The magnetic(for 2) and luminescent(for 3~5) properties were also investigated and discussed.
文摘Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.
基金supported by the National Natural Science Foundation of China(Nos.21573189,21503183 and 21763028)the National College Students’innovation and entrepreneurship training program(D2018)
文摘The reaction of Mn(OAc)2·4 H2 O, 5-ethyl-pyridine-2,3-dicarboxylic acid(H2 epda) and 4,4?-bipyridine(4,4?-bipy)/4,4?-bis(imidazolyl)biphenyl)(bibp) under hydrothermal conditions produced two new manganese(Ⅱ) MOFs [Mn(epda)(4,4?-bipy)1/2](1) and [Mn(epda)(bibp)1/2](2), which were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analyses, and single-crystal X-ray diffraction. The structures of complexes 1 and 2 are similar. In 1, the adjacent Mn(Ⅱ) ions are connected by epda dianion to generate a 2 D(4,4) grid layer, and such 2 D layers are further connected via bibp ligand to form another layer, forming a 2 D pillared-layer. Topologically, the Mn atoms as the node are bridged by the edpa anions and bibp ligands to form a uninodal 5-connected network topology. The magnetic properties of 1 and 2 have also been-investigated, and the exchange interctions were –1.39 and –1.05 cm1, respectively. According to the crystal structures, compounds 1 and 2 were carried out by using hybrid DFT methods at the B3 LYP/6-31 G(d) level. The DFT-BS approach was applied to study the magnetic coupling behaviors for 1 and 2. The result reveals that the calculated exchange coupling constants J were in good agreement with the experimental data.
文摘A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.
基金supported by the Natural Science Foundation of Guangdong Province (No.06300581)
文摘Methyl 3-（5-bromo-l-ethyl-lH-indole-3-carbonyl）aminopropionate has been synthesized by the acylation of 5-bromo-3-trichloroacetylindole with β-alanine methyl ester, followed by alkylation with ethyl iodide, in 82.6% yield. Its crystal structure was gotten and determined by X-ray diffraction method. The crystal is of monoclinic, space group P2/c with a = 11.7927（8）, b = 14.9342（8）, c = 9.0060（5） A, β = 101.558（6）°, V = 1553.93（16） A3, Z = 4, Dc= 1.510 g/cm3, 2 = 0.71073 A,μ（MoKa） = 2.656 mm-1, Mr = 353.22 and F（000） = 720. The structure was refined to R = 0.0401 and wR = 0.0825 for 1704 observed reflections with I 〉 2σ（I）. In the crystal structure, intermolecular N（2）-H（2）...O（1） hydrogen bond and weak intermolecular bonds （C（1）-H（1）...O（1） and C（10）-H（10B）-O（2）） are formed, and π-π stacking also exists.
文摘Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous anti-TNF-α agents have been developed to reduce its circulating levels either by neutralizing, binding or inhibiting the de novo synthesis with the aim of achieving desirable therapeutic effects. In the present study, we compared the effects of a protein-based anti-TNF-α drug, etanercept, and a non-protein-based anti-TNF-α small molecule, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), on the LPS-stimulated secretion of TNF-α in the medium and TNF-α associated with the THP-1 cells in vitro. Both drugs had marked concentration-dependent inhibitory effects on the LPS-stimulated secretion of TNF-α. However, their effects on the LPS-stimulated cell-associated TNF-α were diametrically opposed to each other. For instance, etanercept further increased the level by up to 12-fold, whereas 5-EPP inhibited the level in a dose dependent manner. In addition, 5-EPP caused a significant reduction in the elevated level of cell associated TNF-α caused by LPS + etanercept. The differences in the levels of cell-associated TNF-α as reported in the present study may partly explain the adverse effects of some protein-based anti-TNF-α drugs including etanercept as opposed to a non-protein-based anti-TNF-α drug such as pirfenidone, a structural analogue of 5-EPP, for treatment of some TNF-α mediated diseases. It was concluded from the findings of this study that drugs which elevate the levels of cell associated-TNF-α will potentially have more adverse events even after reducing the secreted levels of TNF-α than the drugs which reduce both the secreted and cell-associated TNF-α levels.
