N-[4-[2-oxo-2-(phenylmethoxyamino)ethyl]phenyl]-2-propylpentanamide | 1026446-03-6

• 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: N-[4-[2-oxo-2-(phenylmethoxyamino)ethyl]phenyl]-2-propylpentanamide
• CAS: 1026446-03-6
• 化学式: C₂₃H₃₀N₂O₃
• 分子量: 382.503
• InChiKey: PELQFCCPPSSMBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[4-[2-oxo-2-(phenylmethoxyamino)ethyl]phenyl]-2-propylpentanamide 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 2-propyl-pentanoic acid (4-hydroxycarbamoylmethyl-phenyl)amide
  参考文献：
  名称：

  Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors

  摘要：

  Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition.

  DOI：

  10.1021/jm0303655
• 作为产物：
  描述：

  对氨基乙酸苯甲酯 在 氢氧化钾 、 TEA 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 生成 N-[4-[2-oxo-2-(phenylmethoxyamino)ethyl]phenyl]-2-propylpentanamide
  参考文献：
  名称：

  Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors

  摘要：

  Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition.

  DOI：

  10.1021/jm0303655

文献信息

• Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors
  作者：Qiang Lu、Ya-Ting Yang、Chang-Shi Chen、Melanie Davis、John C. Byrd、Mark R. Etherton、Asad Umar、Ching-Shih Chen

  DOI：10.1021/jm0303655

  日期：2004.1.1

  Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition.