The stability of imidoyl radicals prepared from 2-(2-alkenyloxy)-phenyl selenoimidates and 2-(2-allylamino)-phenyl selenoimidates and their intramolecular free radical cyclization through the slow addition of tri-N-bu...The stability of imidoyl radicals prepared from 2-(2-alkenyloxy)-phenyl selenoimidates and 2-(2-allylamino)-phenyl selenoimidates and their intramolecular free radical cyclization through the slow addition of tri-N-butyltin hydride and AIBN to obtain 4-chromanones and 4-quinolones were studied. The extension of the methodology to N-phenyl substituted imidoyl selenoates produced tandem cyclizations of the imidoyl radical with the allyl substituent, followed for a second cyclization of the intermediate radical with the aromatic substituent to produce dihydro-chromenoquinolines or tetrahy-dro-dibenzonaphtyridines. Further oxidation with DDQ produced: 6H-chromeno [4,3,b] quinoline and 7-methyl-6H-chromenoquinoline from 2-alkenylamino-phenylbenzamide and 5,6-dihydro-dibenzo [b,h][1,6] naphthyridine and 5,6-dihydro-7-methyl-dibenzo [b,h][1,6] naphthyridine from 2-2-(alkylamino)-N-phenylbenzamides. The cyclization of 2-(N,N-di-prop-2.enylamino)-N-phenylnicotinamide selenoate obtained from 2-aminonicotinic acid, produced 5,6-dihidro-benzo[b]pyrido2,3-h] [1,6] naphthyridine.展开更多
An efficient route to synthesize the heteroaryl-substituted 1,8-naphthyridine derivatives was described. Eight 2-heteroaryl- and 2,7-diheteroaryl-1,8-naphthyridine derivatives were obtained through palladium-catalyzed...An efficient route to synthesize the heteroaryl-substituted 1,8-naphthyridine derivatives was described. Eight 2-heteroaryl- and 2,7-diheteroaryl-1,8-naphthyridine derivatives were obtained through palladium-catalyzed C-N-coupling reactions of chloronaphthyridines with imidazole, benzimidazole, morpholine, 3,5-dimethylpyrazole, and phthalimide in moderate to good yields.展开更多
Four new 1,8-naphthyridine derivatives were synthesized by reacting the parent molecules with aldehydes and characterized. Two of the compounds have completely new and unusual skeletons, and display red-fluorescence e...Four new 1,8-naphthyridine derivatives were synthesized by reacting the parent molecules with aldehydes and characterized. Two of the compounds have completely new and unusual skeletons, and display red-fluorescence emissions and two-photon absorption. Their structures were determined using MS, 1D and 2D NMR, and density functional theory calculations. The structural investigations of 2-methyl-l,8-naphthyridine hydrochloride and hydrobromide showed that abundant hydrogen-bonds and π-π interactions lead to extended networks.展开更多
The title compound（14 S）-2,14-diphenyl-6,6 a,11,12-tetrahydro-5 H,10 H,14 H-[1,8] naphthyridino[1,2-c]pyrido[3,2,1-ij]quinazoline-3-carbonitrile（C31 H26 N4, Mr = 454.56） has been synthesized with 2-aminonicotinald...The title compound（14 S）-2,14-diphenyl-6,6 a,11,12-tetrahydro-5 H,10 H,14 H-[1,8] naphthyridino[1,2-c]pyrido[3,2,1-ij]quinazoline-3-carbonitrile（C31 H26 N4, Mr = 454.56） has been synthesized with 2-aminonicotinaldehyde and 3-oxo-3-phenylpropanenitrile as starting materials, and its crystal structure was determined by single-crystal X-ray diffraction for the first time. The crystal belongs to the triclinic system, space group P1 with a = 8.5833（8）, b = 11.9168（12）, c = 14.4424（14） ？, α = 84.208（3）o, β = 88.427（3）o, γ = 73.704（3）o, V = 1410.7（2） ？3, Z = 2, F（000） = 480, μ = 0.064 mm–1, S = 0.966, the final R = 0.0484 and wR = 0.1388 for 5041 observed reflections with I 〉 2s（I） and 316 variable parameters. The preliminary biological tests show that the title compound has a good antitumor activity against K562 in vitro.展开更多
Ethyl α-（dimethylaminomethylene）-2-cyanomethyl-4-phenylquinoline-3-carboxylate（2） as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl ...Ethyl α-（dimethylaminomethylene）-2-cyanomethyl-4-phenylquinoline-3-carboxylate（2） as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate（1） and N,N-dimethylformamide dimethyl acetal（DMFDMA）.Reaction of this enamine with primary amines（3） in HOAc-DMF at120 ℃then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives（4） in good yields by a tandem addition-elimination-cyclization reaction.展开更多
An efficient method for the synthesis of novel benzo[b]pyrimido[4′,5′：5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet-Spengler cyclization is reported. The reaction of 4-（3-aminopyrimido[4,5-d]thi...An efficient method for the synthesis of novel benzo[b]pyrimido[4′,5′：5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet-Spengler cyclization is reported. The reaction of 4-（3-aminopyrimido[4,5-d]thieno-2-yl）quinoline-2-ones, which could be obtained from Thorpe-Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine,with aromatic aldehydes in the presence of BF3·OEt2 gives pyrimidothieno[1,6]naphthyridines in good yields.展开更多
Naphthyridine-fused bisimidazolium salts were designed and synthesized for the first time. The study of the Cu(Ⅱ) and Pd(Ⅱ) complexes demonstrated that the deprotonated dicarbene ligands are rigid chelating C,C-liga...Naphthyridine-fused bisimidazolium salts were designed and synthesized for the first time. The study of the Cu(Ⅱ) and Pd(Ⅱ) complexes demonstrated that the deprotonated dicarbene ligands are rigid chelating C,C-ligands with strong electron-donating ability in analogy with the classic phenanthroline N,N-ligands.展开更多
The new title compound 8-（（4-（（2,3-diaminopyridin-4-yl）-oxy）-3-fluorophenyl）-amino）-2-（4-fluorophenyl）-3-methyl-2,7-naphthyridin-1（2H）-one（C26H20F2N6O2, Mr = 486.48） has been prepared and determined by s...The new title compound 8-（（4-（（2,3-diaminopyridin-4-yl）-oxy）-3-fluorophenyl）-amino）-2-（4-fluorophenyl）-3-methyl-2,7-naphthyridin-1（2H）-one（C26H20F2N6O2, Mr = 486.48） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/c with a = 15.365（3）, b = 13.144（2）, c = 11.863（2）, β= 108.882（3）°, Z = 4, V = 2267.0（7）3, Dc = 1.425 g/cm3, F（000） = 1008, μ = 0.105 mm-1, MoKa radiation（λ = 0.71073）, R = 0.0480 and wR = 0.1294 for 3197 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that the region C（substituents of 8-amino group and 3-methyl group on the 2,7-naphthyridin-1（2H）-one ring） of compound 6 are effectively planar. Intramolecular and intermolecular hydrogen bonds together with π···π interations are found in the structure. In addition, compound 6 shows potent c-Met and c-Kit kinase inhibition activities.展开更多
This study aimed to design novel 1,8-naphthyridine derivatives as potential anticancer agents that target topoisomerase Ⅱ via a ligand-based drug design strategy.We developed a robust quantitative structure-activity ...This study aimed to design novel 1,8-naphthyridine derivatives as potential anticancer agents that target topoisomerase Ⅱ via a ligand-based drug design strategy.We developed a robust quantitative structure-activity relationship model via multiple linear regression,achieving a coefficient of determination(R 2)of 0.6991.External validation demonstrated high predictive ability,with Q 2(F1)and Q 2(F2)scores of 0.8683 and 0.8670,respectively,indicating substantial reliability in predicting the biological activity of new compounds.Our dataset includes 23 analogs of 1,8-naphthyridine derivatives.The 2-dimensional structures of these compounds were drawn via ChemDraw 15.0 and optimized via density functional theory with the B3LYP hybrid functional approach via Spartan 14.1.Molecular descriptors were calculated via PaDEL software and further processed via Data Pretreatment Software V.WPS 1.2.The Kennard-Stone algorithm in the dataset division graphical user interface 1.2 split the dataset into training and test sets.Docking studies against the DNA topoisomerase Ⅱ receptor(Protein Data Bank ID:1ZXM)revealed substantial interactions,with all the newly designed ligands(L1 to L5)exhibiting superior binding affinities(-9.3 to-8.9 kcal/mol)compared with the existing datasets and the standard drug bevacizumab(-6.0 kcal/mol).The pharmacokinetic evaluation revealed zero violations of Lipinski’s rule of five.Hence,further in-depth in vitro and in vivo investigations are recommended to validate these theoretical findings.展开更多
文摘The stability of imidoyl radicals prepared from 2-(2-alkenyloxy)-phenyl selenoimidates and 2-(2-allylamino)-phenyl selenoimidates and their intramolecular free radical cyclization through the slow addition of tri-N-butyltin hydride and AIBN to obtain 4-chromanones and 4-quinolones were studied. The extension of the methodology to N-phenyl substituted imidoyl selenoates produced tandem cyclizations of the imidoyl radical with the allyl substituent, followed for a second cyclization of the intermediate radical with the aromatic substituent to produce dihydro-chromenoquinolines or tetrahy-dro-dibenzonaphtyridines. Further oxidation with DDQ produced: 6H-chromeno [4,3,b] quinoline and 7-methyl-6H-chromenoquinoline from 2-alkenylamino-phenylbenzamide and 5,6-dihydro-dibenzo [b,h][1,6] naphthyridine and 5,6-dihydro-7-methyl-dibenzo [b,h][1,6] naphthyridine from 2-2-(alkylamino)-N-phenylbenzamides. The cyclization of 2-(N,N-di-prop-2.enylamino)-N-phenylnicotinamide selenoate obtained from 2-aminonicotinic acid, produced 5,6-dihidro-benzo[b]pyrido2,3-h] [1,6] naphthyridine.
基金the National Natural Science Foundation of China （no. 20572096） the Zhejiang Provincial Science Foundation （Grant R405066）.
文摘An efficient route to synthesize the heteroaryl-substituted 1,8-naphthyridine derivatives was described. Eight 2-heteroaryl- and 2,7-diheteroaryl-1,8-naphthyridine derivatives were obtained through palladium-catalyzed C-N-coupling reactions of chloronaphthyridines with imidazole, benzimidazole, morpholine, 3,5-dimethylpyrazole, and phthalimide in moderate to good yields.
文摘Four new 1,8-naphthyridine derivatives were synthesized by reacting the parent molecules with aldehydes and characterized. Two of the compounds have completely new and unusual skeletons, and display red-fluorescence emissions and two-photon absorption. Their structures were determined using MS, 1D and 2D NMR, and density functional theory calculations. The structural investigations of 2-methyl-l,8-naphthyridine hydrochloride and hydrobromide showed that abundant hydrogen-bonds and π-π interactions lead to extended networks.
基金supported by the Natural Science Foundation of Hunan Province(No.2018JJ3196)the opening project of key laboratory of comprehensive utilization of advantage plants resources in Hunan south,Hunan university of science and engineering(No.XNZW17C04,XNZW17C05)aid program for science and technology innovative research team in higher educational institutions of Hunan province(No.2012-318)
文摘The title compound（14 S）-2,14-diphenyl-6,6 a,11,12-tetrahydro-5 H,10 H,14 H-[1,8] naphthyridino[1,2-c]pyrido[3,2,1-ij]quinazoline-3-carbonitrile（C31 H26 N4, Mr = 454.56） has been synthesized with 2-aminonicotinaldehyde and 3-oxo-3-phenylpropanenitrile as starting materials, and its crystal structure was determined by single-crystal X-ray diffraction for the first time. The crystal belongs to the triclinic system, space group P1 with a = 8.5833（8）, b = 11.9168（12）, c = 14.4424（14） ？, α = 84.208（3）o, β = 88.427（3）o, γ = 73.704（3）o, V = 1410.7（2） ？3, Z = 2, F（000） = 480, μ = 0.064 mm–1, S = 0.966, the final R = 0.0484 and wR = 0.1388 for 5041 observed reflections with I 〉 2s（I） and 316 variable parameters. The preliminary biological tests show that the title compound has a good antitumor activity against K562 in vitro.
基金financial support from the Science and Technology Department of Liaoning Province(No.2011220022)
文摘Ethyl α-（dimethylaminomethylene）-2-cyanomethyl-4-phenylquinoline-3-carboxylate（2） as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate（1） and N,N-dimethylformamide dimethyl acetal（DMFDMA）.Reaction of this enamine with primary amines（3） in HOAc-DMF at120 ℃then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives（4） in good yields by a tandem addition-elimination-cyclization reaction.
文摘An efficient method for the synthesis of novel benzo[b]pyrimido[4′,5′：5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet-Spengler cyclization is reported. The reaction of 4-（3-aminopyrimido[4,5-d]thieno-2-yl）quinoline-2-ones, which could be obtained from Thorpe-Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine,with aromatic aldehydes in the presence of BF3·OEt2 gives pyrimidothieno[1,6]naphthyridines in good yields.
基金the National Natural Science Foundation of China (No. 21772134)the Fundamental Research Funds for the Central Universities (No. 20826041D4117)。
文摘Naphthyridine-fused bisimidazolium salts were designed and synthesized for the first time. The study of the Cu(Ⅱ) and Pd(Ⅱ) complexes demonstrated that the deprotonated dicarbene ligands are rigid chelating C,C-ligands with strong electron-donating ability in analogy with the classic phenanthroline N,N-ligands.
基金Project supported by the National Natural Science Foundation of China(No.21272086)
文摘The new title compound 8-（（4-（（2,3-diaminopyridin-4-yl）-oxy）-3-fluorophenyl）-amino）-2-（4-fluorophenyl）-3-methyl-2,7-naphthyridin-1（2H）-one（C26H20F2N6O2, Mr = 486.48） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/c with a = 15.365（3）, b = 13.144（2）, c = 11.863（2）, β= 108.882（3）°, Z = 4, V = 2267.0（7）3, Dc = 1.425 g/cm3, F（000） = 1008, μ = 0.105 mm-1, MoKa radiation（λ = 0.71073）, R = 0.0480 and wR = 0.1294 for 3197 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that the region C（substituents of 8-amino group and 3-methyl group on the 2,7-naphthyridin-1（2H）-one ring） of compound 6 are effectively planar. Intramolecular and intermolecular hydrogen bonds together with π···π interations are found in the structure. In addition, compound 6 shows potent c-Met and c-Kit kinase inhibition activities.
文摘This study aimed to design novel 1,8-naphthyridine derivatives as potential anticancer agents that target topoisomerase Ⅱ via a ligand-based drug design strategy.We developed a robust quantitative structure-activity relationship model via multiple linear regression,achieving a coefficient of determination(R 2)of 0.6991.External validation demonstrated high predictive ability,with Q 2(F1)and Q 2(F2)scores of 0.8683 and 0.8670,respectively,indicating substantial reliability in predicting the biological activity of new compounds.Our dataset includes 23 analogs of 1,8-naphthyridine derivatives.The 2-dimensional structures of these compounds were drawn via ChemDraw 15.0 and optimized via density functional theory with the B3LYP hybrid functional approach via Spartan 14.1.Molecular descriptors were calculated via PaDEL software and further processed via Data Pretreatment Software V.WPS 1.2.The Kennard-Stone algorithm in the dataset division graphical user interface 1.2 split the dataset into training and test sets.Docking studies against the DNA topoisomerase Ⅱ receptor(Protein Data Bank ID:1ZXM)revealed substantial interactions,with all the newly designed ligands(L1 to L5)exhibiting superior binding affinities(-9.3 to-8.9 kcal/mol)compared with the existing datasets and the standard drug bevacizumab(-6.0 kcal/mol).The pharmacokinetic evaluation revealed zero violations of Lipinski’s rule of five.Hence,further in-depth in vitro and in vivo investigations are recommended to validate these theoretical findings.
