2-chloro-1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone | 1310098-52-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-chloro-1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone
• 英文别名: 2-chloro-1-[3-(2-hydroxyphenyl)-5-methyl-3,4-dihydropyrazol-2-yl]ethanone
• CAS: 1310098-52-2
• 化学式: C₁₂H₁₃ClN₂O₂
• 分子量: 252.7
• InChiKey: RFTKFQKTDYTZJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 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：

  2-chloro-1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone 在 4-二甲氨基吡啶 、 硫酸 、 potassium iodide 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 2.0h， 生成 2-[3-methyl-1-(2-(pyrrolidin-1-yl)acetyl)-4,5-dihydro-1H-pyrazol-5-yl]phenyl acetate
  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-(2-hydroxyphenyl)but-3-en-2-one 在 4-二甲氨基吡啶 、 一水合肼 、 对甲苯磺酰氯 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 5.0h， 生成 2-chloro-1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone
  参考文献：
  名称：

  Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents

  摘要：

  A series of novel N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 4a exhibited high activity against human gastric cancer cell SGC-7901, liver cancer Hep-G2 and human prostate PC-3 cell lines with IC50 values of 21.23 +/- 0.99, 29.43 +/- 0.32 and 30.89 +/- 1.07 mu M, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compound 4a can inhibit telomerase with IC50 value of 4.0 +/- 0.32 mu M. Docking simulation was performed to position compound 4a into the telomerase (3DU6) active site to determine the probable binding model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.066

文献信息

• Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo
  作者：Yang Wang、Fei Xiong Cheng、Xiao Long Yuan、Wen Jian Tang、Jing Bo Shi、Chen Zhong Liao、Xin Hua Liu

  DOI：10.1016/j.ejmech.2016.02.009

  日期：2016.4

  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.
• Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents
  作者：Xin-Hua Liu、Ban-Feng Ruan、Jing-Xin Liu、Bao-An Song、Ling-Hong Jing、Jun Li、Yang Yang、Hai-Liang Zhu、Xing-Bao Qi

  DOI：10.1016/j.bmcl.2011.03.066

  日期：2011.5

  A series of novel N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 4a exhibited high activity against human gastric cancer cell SGC-7901, liver cancer Hep-G2 and human prostate PC-3 cell lines with IC50 values of 21.23 +/- 0.99, 29.43 +/- 0.32 and 30.89 +/- 1.07 mu M, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compound 4a can inhibit telomerase with IC50 value of 4.0 +/- 0.32 mu M. Docking simulation was performed to position compound 4a into the telomerase (3DU6) active site to determine the probable binding model. (C) 2011 Elsevier Ltd. All rights reserved.