1-(5-(5-bromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-chloroethanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 1-(5-(5-bromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-chloroethanone
• 英文别名: 1-[3-(5-Bromo-2-hydroxyphenyl)-5-methyl-3,4-dihydropyrazol-2-yl]-2-chloroethanone；1-[3-(5-bromo-2-hydroxyphenyl)-5-methyl-3,4-dihydropyrazol-2-yl]-2-chloroethanone
• 化学式: C₁₂H₁₂BrClN₂O₂
• 分子量: 331.596
• InChiKey: XWTDBKYHGYCFPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(5-(5-bromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-chloroethanone 、 二正丙胺 在 4-二甲氨基吡啶 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以74%的产率得到1-[5-(5-bromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl]-2-(dipropylamino)ethanone
  参考文献：
  名称：

  Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo

  摘要：

  It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 mu M. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.02.009
• 作为产物：
  描述：

  4-(5-溴-2-羟基苯基)丁-3-烯-2-酮 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 1-(5-(5-bromo-2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-chloroethanone
  参考文献：
  名称：

  Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo

  摘要：

  It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 mu M. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.02.009

文献信息

• Identification of human telomerase inhibitors having the core of N -acyl-4,5-dihydropyrazole with anticancer effects
  作者：Xuan Xiao、Yong Ni、Ying-Ming Jia、Min Zheng、Han-Fei Xu、Jun Xu、Chenzhong Liao

  DOI：10.1016/j.bmcl.2016.02.025

  日期：2016.3

  Eight human telomerase inhibitors (5a-5h) having the core of N-acyl-4,5-dihydropyrazole with anticancer effects were identified in this study. Biological results revealed that a few compounds had potent anticancer activities against three common tumor cell lines (SGC-7901, HepG2 and MGC-803). Among them, compound 5c, with a molecular weight of only 272.2 Da, had antiproliferative activities against SGC-7901 and MGC-803 with EC50 values of 2.06 +/- 0.17 and 2.89 +/- 0.62 mu M, respectively, better than 5-Fluorouracil. Compound 5c inhibited the enzyme of telomerase with an IC50 value of 1.86 +/- 0.51 mu M, surpassing the control compound, ethidium bromide. Modeling study showed that this compound can reside in the binding pocket of the telomerase/TNA: DNA hairpin complex. When the moiety of N-acyl was changed to N-sulfonyl, the gotten compounds (8a-8i) had deteriorative activities against both these three cancer cell lines and the enzyme of telomerase. (C) 2016 Elsevier Ltd. All rights reserved.