(S)-3-(4-nitro-phenyl)-2-(7-trityloxycarbamoyl-heptanoylamino)propionic acid methyl ester | 449728-94-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (S)-3-(4-nitro-phenyl)-2-(7-trityloxycarbamoyl-heptanoylamino)propionic acid methyl ester
• 英文别名: methyl (2S)-3-(4-nitrophenyl)-2-[[8-oxo-8-(trityloxyamino)octanoyl]amino]propanoate
• CAS: 449728-94-3
• 化学式: C₃₇H₃₉N₃O₇
• 分子量: 637.733
• InChiKey: WOHWFALAXOQAPU-XIFFEERXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  47
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  140
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-(4-nitro-phenyl)-2-(7-trityloxycarbamoyl-heptanoylamino)propionic acid methyl ester 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以63%的产率得到(S)-2-(7-Hydroxycarbamoyl-heptanoylamino)-3-(4-nitro-phenyl)-propionic acid methyl ester
  参考文献：
  名称：

  Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells

  摘要：

  Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.

  DOI：

  10.1021/jm0208119
• 作为产物：
  描述：

  辛二酸单甲酯 在 N-甲基吗啉 、 lithium hydroxide 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 (S)-3-(4-nitro-phenyl)-2-(7-trityloxycarbamoyl-heptanoylamino)propionic acid methyl ester
  参考文献：
  名称：

  Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells

  摘要：

  Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.

  DOI：

  10.1021/jm0208119

文献信息

• Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells
  作者：Sybille Wittich、Hans Scherf、Changping Xie、Gerald Brosch、Peter Loidl、Clarissa Gerhäuser、Manfred Jung

  DOI：10.1021/jm0208119

  日期：2002.7.1

  Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.