3-(4-chlorophenyl)-1-[(6-chloro-3-pyridinyl)methyl]-N'-[(1E)-(2-hydroxyphenyl)methylidene]-1H-pyrazole-5-carbohydrazide | 1009091-14-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(4-chlorophenyl)-1-[(6-chloro-3-pyridinyl)methyl]-N'-[(1E)-(2-hydroxyphenyl)methylidene]-1H-pyrazole-5-carbohydrazide
• 英文别名: 5-(4-chlorophenyl)-2-[(6-chloropyridin-3-yl)methyl]-N-[(E)-(2-hydroxyphenyl)methylideneamino]pyrazole-3-carboxamide
• CAS: 1009091-14-8
• 化学式: C₂₃H₁₇Cl₂N₅O₂
• 分子量: 466.326
• InChiKey: DRRUJWFFGWHRTE-UVHMKAGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  92.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氯-5-氯甲基吡啶 在 potassium carbonate 、 一水合肼 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 5.5h， 生成 3-(4-chlorophenyl)-1-[(6-chloro-3-pyridinyl)methyl]-N'-[(1E)-(2-hydroxyphenyl)methylidene]-1H-pyrazole-5-carbohydrazide
  参考文献：
  名称：

  Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis

  摘要：

  Using literature data on anticancer activity of pyrazole derivatives, 3D-QSAR models were developed and 3D-QSAR analysis was performed. The 3D-QSAR analysis enabled identification of molecular properties that have the highest impact on antitumor activity against lung cancer cells. The results of 3D-QSAR analysis were taken into account while new compounds were designed. Obtained 3D-QSAR models were used for prediction of activity of new compounds. In this way, design of new compounds was guided by 3D-QSAR analysis which was performed on literature data. Ten new pyrazole derivatives were synthesised and their antitumor activities against A549 and NCIH23 lung cancer cells were validated. In order to obtain full profile of anticancer activity, cells viability (MTS) assays were combined with cell proliferation (BrdU) assays which measure actively dividing cells in treated sample. Experimental measurements showed good agreement between predicted and measured activities for majority of compounds. Also, anticancer activities of new pyrazole derivatives pointed to the chemical groups that can be useful in designing antitumor molecules. Substitution of hydrazine linker with rigid, 1,2,4-oxadiazole moiety resulted in compound 10, which has low (if any) cytotoxic activity and high potential cytostatic activity. Therefore, compound 10 presents a good starting point for design of new, more potent and safer anticancer therapeutics. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.032

文献信息

• Synthesis and structure–activity relationships of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone derivatives as potential agents against A549 lung cancer cells
  作者：Yong Xia、Chuan-Dong Fan、Bao-Xiang Zhao、Jing Zhao、Dong-Soo Shin、Jun-Ying Miao

  DOI：10.1016/j.ejmech.2008.01.021

  日期：2008.11

  A series of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone derivatives were synthesized and the effects of all the compounds on A549 cell growth were investigated. The results showed that all compounds had almost inhibitory effects on the growth of A549 cells. The study on structure-activity relationships and prediction of lipophilicities of compounds showed that compounds with Log P values in the range of 4.12-6.80 had inhibitory effects on the growth of A549 cells, and among of them the hydrazone derived from salicylaldehyde had much more inhibitory effects. (C) 2008 Elsevier Masson SAS. All rights reserved.