Aryl halides are a kind of extremely valuable compounds used in transition-metal-catalyzed coupling reactions, as well as important structure motifs in many natural products and manufactured drugs. The classical appro...Aryl halides are a kind of extremely valuable compounds used in transition-metal-catalyzed coupling reactions, as well as important structure motifs in many natural products and manufactured drugs. The classical approach for preparation of haloarenes is electrophilic aromatic substitution（EAS） using various halogenating reagents or oxidative halogenations with halogenating reagent generated in situ from halides and oxidants, such as peroxide, oxygen and meta-cholorperoxybenzoic acid（mCPBA）. However, harsh reaction conditions are required for halogenation of less active aromatics, orthoMetalation followed by halogen quenching is another approach for halogenation of aromatics. However, there are obvious drawbacks for these methods, such as low regioselectivity, harsh conditions and even dangerous procedures. Therefore, the development of an alternative and practical way remains challenge in organic synthesis.展开更多
Based on our previous researches, a novel phenylpyrimidine pharmacophore model was proposed and fifteen derivatives were synthesized and characterized by means of spectroscopy methods. The inhibitory effects of them w...Based on our previous researches, a novel phenylpyrimidine pharmacophore model was proposed and fifteen derivatives were synthesized and characterized by means of spectroscopy methods. The inhibitory effects of them were screened against HeLa cell line by virtue of MTT assay in vitro. The results indicate some of the phenyl- pyrimidine derivatives exhibit potent biological activities. Among them, compounds 6g and 6h exhibit the best activity at half maximal inhibitory concentrations of 1.5 and 2.8 μmol/L, respectively. These compotmds also exhibit good activities against HepG2 cell line and MCF-7 cell line. FLT-3 kinase was screened as the most potent molecular target. Computational docking between compound 6g and FLT-3 was carried ont to interpret the binding mode. The results show phenylpyrimidine derivatives have effective antitumor activities, which provides a base for further research of them as antitumor agents.展开更多
Liquid crystals containing phenylpyrimidine units are the fascination condensed state of soft matter with unique electrical, optical and mechanical properties. In this paper, a novel and efficient route was reported f...Liquid crystals containing phenylpyrimidine units are the fascination condensed state of soft matter with unique electrical, optical and mechanical properties. In this paper, a novel and efficient route was reported for the synthesis of N-（3-（dimethylamino）-2-（4-ethoxyphenyl）allylidene）-N-methylmethanaminium perchlorate by the WillgerodtKindler reaction, which can be further applied to prepare liquid crystals containing phenylpyrimidine units. The product was confirmed by JHNMR, MS, FT-IR and elemental analysis. The experimental conditions of the Willgerodt-Kindler reaction were also studied and the results show that the yield of p-ethoxyphenyl-acetic acid increased remarkably with a reaction time up to 60 rain, then decreased due to carbonization. On the other hand, the yield was also influenced by microwave power. It increased from 20.6 % to 78.8 % with a rise in the microwave power from 250 W to 450 W, but the product was carbonized at 640 W.展开更多
目的合成一系列嘧啶联苯类化合物,测试其对8-羟基鸟嘌呤核苷酸酶(Mut T homolog 1,MTH1酶)和癌细胞增殖的体外抑制活性。方法以对溴硝基苯和二氯嘧啶为起始原料,经Suzuki偶联、铁酸还原和取代等反应得到4个目标化合物。酶实验根据MTH1...目的合成一系列嘧啶联苯类化合物,测试其对8-羟基鸟嘌呤核苷酸酶(Mut T homolog 1,MTH1酶)和癌细胞增殖的体外抑制活性。方法以对溴硝基苯和二氯嘧啶为起始原料,经Suzuki偶联、铁酸还原和取代等反应得到4个目标化合物。酶实验根据MTH1酶水解d GTP的特性,结合分光光度法,计算酶抑制率。细胞实验选用SW480和Hep G2细胞株,采用MTT法测定。结果与结论化合物6a-1、6a-2、6a-3、4b具有体外MTH1酶抑制活性,化合物3a、5a-1、5a-3、6a-1、6a-2、6a-3、3b、4b具有一定癌细胞增殖抑制活性。展开更多
A number of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines were synthesized. The structures of these new compounds were confirmed by ^1H NMR, IR and elemental analysis. Biological evalua...A number of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines were synthesized. The structures of these new compounds were confirmed by ^1H NMR, IR and elemental analysis. Biological evaluation in the greenhouse showed several compounds have good fungicidal activities at 25 mg/L.展开更多
Previous studies have shown that Ras/Raf/MEK/ERK signaling pathway is up-regulated in almost all cancer cells.Blocking of this pathway by MEK inhibition is an efficient therapeutic approach of cancer.In the present st...Previous studies have shown that Ras/Raf/MEK/ERK signaling pathway is up-regulated in almost all cancer cells.Blocking of this pathway by MEK inhibition is an efficient therapeutic approach of cancer.In the present study,we described the discovery of 5-benzyl-2-phenylpyrimidin-4（3 H）-one as a novel skeleton of allosteric MEK inhibitor.All acquired target compounds exhibited modest potency to inhibit MEK1 in Raf-MEK cascading assay,and docking studies revealed that the binding mode of the most potent compound（SJ3） was very similar to that of the well known diarylamine-based inhibitor（PD0325901）.The results provided valuable guidance for further optimizations on this novel scaffold to achieve druggable molecules.展开更多
文摘Aryl halides are a kind of extremely valuable compounds used in transition-metal-catalyzed coupling reactions, as well as important structure motifs in many natural products and manufactured drugs. The classical approach for preparation of haloarenes is electrophilic aromatic substitution（EAS） using various halogenating reagents or oxidative halogenations with halogenating reagent generated in situ from halides and oxidants, such as peroxide, oxygen and meta-cholorperoxybenzoic acid（mCPBA）. However, harsh reaction conditions are required for halogenation of less active aromatics, orthoMetalation followed by halogen quenching is another approach for halogenation of aromatics. However, there are obvious drawbacks for these methods, such as low regioselectivity, harsh conditions and even dangerous procedures. Therefore, the development of an alternative and practical way remains challenge in organic synthesis.
基金Supported by the Youth Natural Science Foundation of Heilongjiang Province, China（No.QC2016025）, the University Nursing Programs for Young Scholars with Creative Talents in Heilongjiang Province, China（No.UNPYSCT-2017003） and the ＂Young Talents＂ Project of Northeast Agricultural University, China （No. 17QC13）.
文摘Based on our previous researches, a novel phenylpyrimidine pharmacophore model was proposed and fifteen derivatives were synthesized and characterized by means of spectroscopy methods. The inhibitory effects of them were screened against HeLa cell line by virtue of MTT assay in vitro. The results indicate some of the phenyl- pyrimidine derivatives exhibit potent biological activities. Among them, compounds 6g and 6h exhibit the best activity at half maximal inhibitory concentrations of 1.5 and 2.8 μmol/L, respectively. These compotmds also exhibit good activities against HepG2 cell line and MCF-7 cell line. FLT-3 kinase was screened as the most potent molecular target. Computational docking between compound 6g and FLT-3 was carried ont to interpret the binding mode. The results show phenylpyrimidine derivatives have effective antitumor activities, which provides a base for further research of them as antitumor agents.
文摘Liquid crystals containing phenylpyrimidine units are the fascination condensed state of soft matter with unique electrical, optical and mechanical properties. In this paper, a novel and efficient route was reported for the synthesis of N-（3-（dimethylamino）-2-（4-ethoxyphenyl）allylidene）-N-methylmethanaminium perchlorate by the WillgerodtKindler reaction, which can be further applied to prepare liquid crystals containing phenylpyrimidine units. The product was confirmed by JHNMR, MS, FT-IR and elemental analysis. The experimental conditions of the Willgerodt-Kindler reaction were also studied and the results show that the yield of p-ethoxyphenyl-acetic acid increased remarkably with a reaction time up to 60 rain, then decreased due to carbonization. On the other hand, the yield was also influenced by microwave power. It increased from 20.6 % to 78.8 % with a rise in the microwave power from 250 W to 450 W, but the product was carbonized at 640 W.
文摘A number of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines were synthesized. The structures of these new compounds were confirmed by ^1H NMR, IR and elemental analysis. Biological evaluation in the greenhouse showed several compounds have good fungicidal activities at 25 mg/L.
基金National Natural Science Fund of China(Grant No.21172012)the Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20120001110010)Beijing Natural Science Foundation of China(Grant No.7162110)
文摘Previous studies have shown that Ras/Raf/MEK/ERK signaling pathway is up-regulated in almost all cancer cells.Blocking of this pathway by MEK inhibition is an efficient therapeutic approach of cancer.In the present study,we described the discovery of 5-benzyl-2-phenylpyrimidin-4（3 H）-one as a novel skeleton of allosteric MEK inhibitor.All acquired target compounds exhibited modest potency to inhibit MEK1 in Raf-MEK cascading assay,and docking studies revealed that the binding mode of the most potent compound（SJ3） was very similar to that of the well known diarylamine-based inhibitor（PD0325901）.The results provided valuable guidance for further optimizations on this novel scaffold to achieve druggable molecules.
