7-{3-[1-(3,5-difluorophenyl)-1H-[1,2,3]triazol-4-yl]phenylcarbamoyl}heptanoic acid methyl ester | 1204006-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-{3-[1-(3,5-difluorophenyl)-1H-[1,2,3]triazol-4-yl]phenylcarbamoyl}heptanoic acid methyl ester
• 英文别名: Methyl 8-[3-[1-(3,5-difluorophenyl)triazol-4-yl]anilino]-8-oxooctanoate
• CAS: 1204006-04-1
• 化学式: C₂₃H₂₄F₂N₄O₃
• 分子量: 442.465
• InChiKey: AZMHOHGPLQHXDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  86.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-{3-[1-(3,5-difluorophenyl)-1H-[1,2,3]triazol-4-yl]phenylcarbamoyl}heptanoic acid methyl ester 在 羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以41%的产率得到octanedioic acid {3-[1-(3,5-difluorophenyl)-1H-[1,2,3]triazol-4-yl]phenyl}amide hydroxyamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Triazol-4-ylphenyl-Bearing Histone Deacetylase Inhibitors as Anticancer Agents

  摘要：

  Our triazole-based histone deacetylase inhibitor (HDACI), octanedioic acid hydroxyamide[3-(1-phenyl-1H-[1,2,3]triazol-4-yl)phenyl]amide (4a), suppresses pancreatic cancer cell growth in vitro with the lowest IC50 value of 20 nM against MiaPaca-2 cell. In this study, we continued our efforts to develop triazol-4-ylphenyl bearing hydroxamate analogues by embellishing the terminal phenyl ring of 4a with different substituents. The isoform inhibitory profile of these hydroxamate analogues was similar to those of 4a. All of these triazol-4-ylphenyl bearing hydroxamates are pan-HDACIs like SAHA. Moreover, compounds 4h and 11a were found to be very effective inhibitors of cancer cell growth in the HupT3 (IC50 = 50 nM) and MiaPaca-2 (IC50 = 40 nM) cancer cell lines, respectively. Compound 4a was found to reactivate the expression of CDK inhibitor proteins and to suppress pancreatic cancer cell growth in vivo. Taken together, these data further support the value of the triazol-4-ylphenyl bearing hydroxamates in identifying potential pancreatic cancer therapies.

  DOI：

  10.1021/jm901667k
• 作为产物：
  描述：

  7-(3-乙炔基苯基氨基甲酰基)庚酸甲酯 、 3,5-difluorophenyl azide 在 copper(ll) sulfate pentahydrate 、 (+)-sodium-L-ascorbate 作用下， 以 乙醇 、 水 为溶剂， 以59%的产率得到7-{3-[1-(3,5-difluorophenyl)-1H-[1,2,3]triazol-4-yl]phenylcarbamoyl}heptanoic acid methyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Triazol-4-ylphenyl-Bearing Histone Deacetylase Inhibitors as Anticancer Agents

  摘要：

  Our triazole-based histone deacetylase inhibitor (HDACI), octanedioic acid hydroxyamide[3-(1-phenyl-1H-[1,2,3]triazol-4-yl)phenyl]amide (4a), suppresses pancreatic cancer cell growth in vitro with the lowest IC50 value of 20 nM against MiaPaca-2 cell. In this study, we continued our efforts to develop triazol-4-ylphenyl bearing hydroxamate analogues by embellishing the terminal phenyl ring of 4a with different substituents. The isoform inhibitory profile of these hydroxamate analogues was similar to those of 4a. All of these triazol-4-ylphenyl bearing hydroxamates are pan-HDACIs like SAHA. Moreover, compounds 4h and 11a were found to be very effective inhibitors of cancer cell growth in the HupT3 (IC50 = 50 nM) and MiaPaca-2 (IC50 = 40 nM) cancer cell lines, respectively. Compound 4a was found to reactivate the expression of CDK inhibitor proteins and to suppress pancreatic cancer cell growth in vivo. Taken together, these data further support the value of the triazol-4-ylphenyl bearing hydroxamates in identifying potential pancreatic cancer therapies.

  DOI：

  10.1021/jm901667k