3-[benzyloxy(7-methyloctanoyl)amino]propanoic acid tert-butyl ester | 1239468-38-2

• 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: 3-[benzyloxy(7-methyloctanoyl)amino]propanoic acid tert-butyl ester
• 英文别名: tert-butyl 3-[benzyloxy(7-methyloctanoyl)amino]propanoate；Tert-butyl 3-[7-methyloctanoyl(phenylmethoxy)amino]propanoate
• CAS: 1239468-38-2
• 化学式: C₂₃H₃₇NO₄
• 分子量: 391.551
• InChiKey: MGOGNJMSKJMDOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[benzyloxy(7-methyloctanoyl)amino]propanoic acid tert-butyl ester 在 5% Pd(II)/C(eggshell) 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 以82%的产率得到3-[hydroxy(7-methyloctanoyl)amino]propanoic acid tert-butyl ester
  参考文献：
  名称：

  Design, Synthesis, Enzyme-Inhibitory Activity, and Effect on Human Cancer Cells of a Novel Series of Jumonji Domain-Containing Protein 2 Histone Demethylase Inhibitors

  摘要：

  Selective inhibitors of Jumonji domain-containing protein (JMJD) histone demethylases are candidate anticancer agents as well as potential tools for elucidating the biological functions of JMJDs. On the basis of the crystal structure of JMJD2A and a homology model of JMJD2C, we designed and prepared a series of hydroxamate analogues bearing a tertiary amine. Enzyme assays using JMJD2C, JMJD2A, and prolyl hydroxylases revealed that hydroxamate analogue 8 is a potent and selective JMJD2 inhibitor, showing 500-fold greater JMJD2C-inhibitory activity and more than 9100-fold greater JMJD2C-selectivity compared with the lead compound N-oxalylglycine 2. Compounds 17 and 18, prodrugs of compound 8, each showed synergistic growth inhibition of cancer cells in combination with an inhibitor of lysine-specific demethylase I (LSD1). These findings suggest that combination treatment with JMJD2 inhibitors and LSD I inhibitors may represent a novel strategy for anticancer chemotherapy.

  DOI：

  10.1021/jm1003655
• 作为产物：
  描述：

  7-methyloctanoyl chloride 、 tert-butyl 3-(benzyloxyamino)propanoate 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以1.36 g的产率得到3-[benzyloxy(7-methyloctanoyl)amino]propanoic acid tert-butyl ester
  参考文献：
  名称：

  Design, Synthesis, Enzyme-Inhibitory Activity, and Effect on Human Cancer Cells of a Novel Series of Jumonji Domain-Containing Protein 2 Histone Demethylase Inhibitors

  摘要：

  Selective inhibitors of Jumonji domain-containing protein (JMJD) histone demethylases are candidate anticancer agents as well as potential tools for elucidating the biological functions of JMJDs. On the basis of the crystal structure of JMJD2A and a homology model of JMJD2C, we designed and prepared a series of hydroxamate analogues bearing a tertiary amine. Enzyme assays using JMJD2C, JMJD2A, and prolyl hydroxylases revealed that hydroxamate analogue 8 is a potent and selective JMJD2 inhibitor, showing 500-fold greater JMJD2C-inhibitory activity and more than 9100-fold greater JMJD2C-selectivity compared with the lead compound N-oxalylglycine 2. Compounds 17 and 18, prodrugs of compound 8, each showed synergistic growth inhibition of cancer cells in combination with an inhibitor of lysine-specific demethylase I (LSD1). These findings suggest that combination treatment with JMJD2 inhibitors and LSD I inhibitors may represent a novel strategy for anticancer chemotherapy.

  DOI：

  10.1021/jm1003655