7-(3-乙炔基苯基氨基甲酰基)庚酸甲酯 | 1033391-32-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 7-(3-乙炔基苯基氨基甲酰基)庚酸甲酯
• 英文名称: 7-(3-ethynylphenylcarbamoyl)heptanoic acid methyl ester
• 英文别名: methyl 8-((3-ethynylphenyl)amino)-8-oxooctanoate
• CAS: 1033391-32-0
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: INJQWMCSZIPKPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.12
• 重原子数：
  21.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  55.4
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  7-(3-乙炔基苯基氨基甲酰基)庚酸甲酯 在 盐酸羟胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 24.0h， 以17%的产率得到N1-(3-ethynylphenyl)-N8-hydroxyoctanediamide
  参考文献：
  名称：

  BIFUNCTION CHEMICAL EPIGENENTIC MODIFIERS AND METHODS OF USE

  摘要：

  本公开涉及双功能化学表观遗传修饰剂，以及制备方法、工具包和使用双功能化学表观遗传修饰剂的方法。双功能化学表观遗传修饰剂可以包括FK506分子或其衍生物，连接剂和双功能配体。双功能配体可以是组蛋白去乙酰化酶抑制剂。

  公开号：

  US20210355476A1
• 作为产物：
  描述：

  辛二酸单甲酯 、 3-氨基苯乙炔 在 吡啶 、 三氯氧磷 作用下， 反应 0.5h， 以37%的产率得到7-(3-乙炔基苯基氨基甲酰基)庚酸甲酯
  参考文献：
  名称：

  A Series of Potent and Selective, Triazolylphenyl-Based Histone Deacetylases Inhibitors with Activity against Pancreatic Cancer Cells and Plasmodium falciparum

  摘要：

  The discovery of the rules governing the inhibition of the various HDAC isoforms is likely to be key to identifying improved therapeutics that act as epigenetic modulators of gene transcription. Herein we present results on the modification of the CAP region of a set of triazolylphenyl-based HDACIs, and show that the nature of substitution on the phenyl ring plays a role in their selectivity for HDAC1 versus HDAC6, with low to moderate selectivity (2-51-fold) being achieved. In light of the valuable selectivity and potency that were identified for the triazolylphenyl ligand 6b in the inhibition of HDAC6 (IC50 = 1.9 nM), this compound represents a valuable research tool and a candidate for further chemical modifications. Lastly, these new HDACIs were studied for both their anticancer and antimalarial activity, which serve to validate the superior activity of the HDACI 10c.

  DOI：

  10.1021/jm701606b

文献信息

• Synthesis and Biological Evaluation of Triazol-4-ylphenyl-Bearing Histone Deacetylase Inhibitors as Anticancer Agents
  作者：Rong He、Yufeng Chen、Yihua Chen、Andrei V. Ougolkov、Jin-San Zhang、Doris N. Savoy、Daniel D. Billadeau、Alan P. Kozikowski

  DOI：10.1021/jm901667k

  日期：2010.2.11

  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.