目的运用Discovery Studio 2018软件的反向找靶功能,对设计的一类3-芳基-5-芳甲酰胺基吡唑-4-乙酰胺衍生物进行药物潜在靶点预测和筛选。方法以取代的苯甲酸甲酯为起始原料,经过亲核加成-消除、亲核取代、缩合等四步反应得到目标化合物...目的运用Discovery Studio 2018软件的反向找靶功能,对设计的一类3-芳基-5-芳甲酰胺基吡唑-4-乙酰胺衍生物进行药物潜在靶点预测和筛选。方法以取代的苯甲酸甲酯为起始原料,经过亲核加成-消除、亲核取代、缩合等四步反应得到目标化合物。根据靶点筛选结果,用MTT法对其体外抗肿瘤活性进行初步筛选。结果与结论共合成了10个目标化合物,均为新化合物,其结构经1H-NMR、13C-NM R及HRMS谱确证。化合物5a^5h均具有一定的抗肿瘤活性,其中化合物5h的活性最佳,对人骨肉瘤细胞Saos-2和U-2 OS的抗增殖活性的IC50值分别是1. 3μmol·L^-1和0. 9μmol·L^-1。展开更多
An efficient route for the palladium-catalyzed reductive aminocarbonylation of olefins with nitroarenes was developed using carbon monoxide(CO)as both reductant and carbonyl source,which enables facile access to amide...An efficient route for the palladium-catalyzed reductive aminocarbonylation of olefins with nitroarenes was developed using carbon monoxide(CO)as both reductant and carbonyl source,which enables facile access to amides with excellent regioselectivity and broad substrate scope.It is found that the counter anions of the Pd catalyst precursors significantly affect the reaction chemoselectivity and amide regioselectivity.Branched amides were mainly obtained with K2PdCl4 as the metal catalyst,and phosphine ligands had no influence on the regioselectivity but affected the catalytic reactivity.However,phosphine ligands had significant effects on aminocarbonylation regioselectivity when Pd(CH3CN)4(OTf)2 was used;monodentate phosphines tended to form branched amides,and bidentate phosphines mainly formed linear amides.Trapping experiments,primary kinetic studies,and control reactions with all possible N-species reduced from nitroarene indicated that the catalytic synthesis of branched and linear amides produced nitrene(further converted to enamide)and aniline,respectively,different from the previous ligand-controlled regioselective synthesis of amides via the aminocarbonylation of olefins with amines.Furthermore,the proposed synthesis route could be applied in the synthesis of gram-scale propanil under mild conditions.展开更多
The strain rate effects of aramid fiber material, quasi-static and ballistic impact perforation of composite laminates made of aramid fabric and phenolic resin/PVB are investigated respectively by means of MTS, split ...The strain rate effects of aramid fiber material, quasi-static and ballistic impact perforation of composite laminates made of aramid fabric and phenolic resin/PVB are investigated respectively by means of MTS, split Hopkinson tension bars and ballistic impact apparatus. The tensile impact experiments on aramid fiber material are performed in strain rate range from 0.01/s to 1000/s. Experimental results show that the mechanical properties of aramid fiber material are insensitive to strain rate in the range from 0. 01/s to 1 000/s. An energy model to predict final velocity of composite laminates subjected to ballistic impact is proposed on the basis of experimental data of quasi-static perforation through the targets. The predicted final velocities show good agreement with the experimental final velocity.展开更多
Carboxylate as a promising and valuable directing group has attracted a great deal of attention.However,employing it as a traceless direction group has rarely been reported.We developed the ruthenium-catalyzed amidati...Carboxylate as a promising and valuable directing group has attracted a great deal of attention.However,employing it as a traceless direction group has rarely been reported.We developed the ruthenium-catalyzed amidation of substituted benzoic acids with isocyanates via directed C–H functionalization followed by decarboxylation to afford the corresponding metasubstituted N-aryl benzamides,in which the carboxylate serves as a unique,removable directing group.Notably,this protocol can provide an efficient alternative to access meta-substituted N-aryl benzamides,which are much more difficult to prepare than ortho-substituted analogues.展开更多
文摘An efficient route for the palladium-catalyzed reductive aminocarbonylation of olefins with nitroarenes was developed using carbon monoxide(CO)as both reductant and carbonyl source,which enables facile access to amides with excellent regioselectivity and broad substrate scope.It is found that the counter anions of the Pd catalyst precursors significantly affect the reaction chemoselectivity and amide regioselectivity.Branched amides were mainly obtained with K2PdCl4 as the metal catalyst,and phosphine ligands had no influence on the regioselectivity but affected the catalytic reactivity.However,phosphine ligands had significant effects on aminocarbonylation regioselectivity when Pd(CH3CN)4(OTf)2 was used;monodentate phosphines tended to form branched amides,and bidentate phosphines mainly formed linear amides.Trapping experiments,primary kinetic studies,and control reactions with all possible N-species reduced from nitroarene indicated that the catalytic synthesis of branched and linear amides produced nitrene(further converted to enamide)and aniline,respectively,different from the previous ligand-controlled regioselective synthesis of amides via the aminocarbonylation of olefins with amines.Furthermore,the proposed synthesis route could be applied in the synthesis of gram-scale propanil under mild conditions.
基金Science and Technology Foundation of Ministry of Education of China ( DF 02064).
文摘The strain rate effects of aramid fiber material, quasi-static and ballistic impact perforation of composite laminates made of aramid fabric and phenolic resin/PVB are investigated respectively by means of MTS, split Hopkinson tension bars and ballistic impact apparatus. The tensile impact experiments on aramid fiber material are performed in strain rate range from 0.01/s to 1000/s. Experimental results show that the mechanical properties of aramid fiber material are insensitive to strain rate in the range from 0. 01/s to 1 000/s. An energy model to predict final velocity of composite laminates subjected to ballistic impact is proposed on the basis of experimental data of quasi-static perforation through the targets. The predicted final velocities show good agreement with the experimental final velocity.
基金supported by the National Natural Science Foundation of China(20906059,21272145)the Shaanxi Innovative Team of Key Science and Technology(2013KCT-17)+1 种基金the Fundamental Research Funds for the Central Universities(GK201503030,GK261001095)the 111 Project,and Canada Research Chair(to CJL)
文摘Carboxylate as a promising and valuable directing group has attracted a great deal of attention.However,employing it as a traceless direction group has rarely been reported.We developed the ruthenium-catalyzed amidation of substituted benzoic acids with isocyanates via directed C–H functionalization followed by decarboxylation to afford the corresponding metasubstituted N-aryl benzamides,in which the carboxylate serves as a unique,removable directing group.Notably,this protocol can provide an efficient alternative to access meta-substituted N-aryl benzamides,which are much more difficult to prepare than ortho-substituted analogues.
