7-(4-nitrobenzoylamino)-heptanoic acid methyl ester | 1036742-52-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 7-(4-nitrobenzoylamino)-heptanoic acid methyl ester
• 英文别名: methyl 7-(4-nitrobenzamido)heptanoate；Methyl 7-[(4-nitrobenzoyl)amino]heptanoate
• CAS: 1036742-52-5
• 化学式: C₁₅H₂₀N₂O₅
• 分子量: 308.334
• InChiKey: ZKYGUTIYHMPNMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-(4-nitrobenzoylamino)-heptanoic acid methyl ester 在 potassium cyanide 、 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 palladium 10% on activated carbon 、 氢气 、 羟胺 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 19.5h， 生成 FITC-4-(((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-N-(7-(hydroxy-amino)-7-oxoheptyl)benzamide
  参考文献：
  名称：

  Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia

  摘要：

  The HDAC inhibitor 4-tert-butyl-N-(4-(hydroxycarbamoyl)phenyl)benzamide (AES-350, 51) was identified as a promising preclinical candidate for the treatment of acute myeloid leukemia (AML), an aggressive malignancy with a meagre 24% 5-year survival rate. Through screening of low-molecular-weight analogues derived from the previously discovered novel HDAC inhibitor, AES-135, compound 51 demonstrated greater HDAC isoform selectivity, higher cytotoxicity in MV4-11 cells, an improved therapeutic window, and more efficient absorption through cellular and lipid membranes. Compound 51 also demonstrated improved oral bioavailability compared to SAHA in mouse models. A broad spectrum of experiments, including FACS, ELISA, and Western blotting, were performed to support our hypothesis that 51 dose-dependently triggers apoptosis in AML cells through HDAC inhibition.

  DOI：

  10.1021/acsmedchemlett.9b00471
• 作为产物：
  描述：

  7-氨基庚酸 在 N-甲基吗啉 、 氯化亚砜 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 8.42h， 生成 7-(4-nitrobenzoylamino)-heptanoic acid methyl ester
  参考文献：
  名称：

  Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia

  摘要：

  The HDAC inhibitor 4-tert-butyl-N-(4-(hydroxycarbamoyl)phenyl)benzamide (AES-350, 51) was identified as a promising preclinical candidate for the treatment of acute myeloid leukemia (AML), an aggressive malignancy with a meagre 24% 5-year survival rate. Through screening of low-molecular-weight analogues derived from the previously discovered novel HDAC inhibitor, AES-135, compound 51 demonstrated greater HDAC isoform selectivity, higher cytotoxicity in MV4-11 cells, an improved therapeutic window, and more efficient absorption through cellular and lipid membranes. Compound 51 also demonstrated improved oral bioavailability compared to SAHA in mouse models. A broad spectrum of experiments, including FACS, ELISA, and Western blotting, were performed to support our hypothesis that 51 dose-dependently triggers apoptosis in AML cells through HDAC inhibition.

  DOI：

  10.1021/acsmedchemlett.9b00471

文献信息

• Development of a fluorescence polarization based assay for histone deacetylase ligand discovery
  作者：Ralph Mazitschek、Vishal Patel、Dyann F. Wirth、Jon Clardy

  DOI：10.1016/j.bmcl.2008.04.007

  日期：2008.5

  pursued as cancer chemotherapeutics but may be useful in treating psychiatric disorders, malaria, and other diseases. Herein, we describe an inexpensive and robust assay, based on fluorescence polarization, for HDAC ligand discovery. The assay is well suited for high-throughput screening and enzyme kinetic studies.

  组蛋白去乙酰化酶 (HDAC) 调节许多重要的生理过程，调节 HDAC 活性的小分子的发现具有学术和临床意义。HDAC 抑制剂，尤其是 SAHA，已被用作癌症化学治疗剂，但可用于治疗精神障碍、疟疾和其他疾病。在此，我们描述了一种基于荧光偏振的廉价且稳健的检测，用于 HDAC 配体发现。该测定非常适合高通量筛选和酶动力学研究。