(S)-{4-Boc-amino-1-[(4-methyl-2-oxo-2H-chromen-7-ylcarbamoyl)methyl]butyl}carbamic acid benzyl ester | 787549-19-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: (S)-{4-Boc-amino-1-[(4-methyl-2-oxo-2H-chromen-7-ylcarbamoyl)methyl]butyl}carbamic acid benzyl ester
• 英文别名: benzyl N-[(3S)-1-[(4-methyl-2-oxochromen-7-yl)amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxohexan-3-yl]carbamate
• CAS: 787549-19-3
• 化学式: C₂₉H₃₅N₃O₇
• 分子量: 537.613
• InChiKey: GVLWYDODJGXPHO-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-{4-Boc-amino-1-[(4-methyl-2-oxo-2H-chromen-7-ylcarbamoyl)methyl]butyl}carbamic acid benzyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Subtype Selective Substrates for Histone Deacetylases

  摘要：

  To probe the steric requirements for deacylation, we synthesized lysine-derived small molecule substrates and examined structure -reactivity relationships with various histone deacetylases. Rat liver, human HeLa, and human recombinant class I and II histone deacetylases (HDACs) as well as human recombinant NAD(+)-dependent SIRT1 (class III enzyme) were used in these studies. A benzyloxycarbonyl substituent on the alpha-amino group yielded the highest conversion rates. Replacing the epsilon-acetyl group with larger lipophilic acyl substituents led to a pronounced decrease in conversion by class I and II enzymes; the class III enzyme displayed a greater tolerance. Incubations with recombinant FLAG-tagged human HDACs 1, 3, and 6 showed a distinct subtype selectivity among small molecule substrates. The subtype selectivity of HDAC inhibitors could be predicted with these substrates and an easily obtainable mixture of HDAC subtypes.

  DOI：

  10.1021/jm0497592
• 作为产物：
  描述：

  7-氨基-4-甲基香豆素 、 N-α-benzyloxycarbonyl-N-ε-(Boc)-β-lysine 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 2.42h， 以31%的产率得到(S)-{4-Boc-amino-1-[(4-methyl-2-oxo-2H-chromen-7-ylcarbamoyl)methyl]butyl}carbamic acid benzyl ester
  参考文献：
  名称：

  Subtype Selective Substrates for Histone Deacetylases

  摘要：

  To probe the steric requirements for deacylation, we synthesized lysine-derived small molecule substrates and examined structure -reactivity relationships with various histone deacetylases. Rat liver, human HeLa, and human recombinant class I and II histone deacetylases (HDACs) as well as human recombinant NAD(+)-dependent SIRT1 (class III enzyme) were used in these studies. A benzyloxycarbonyl substituent on the alpha-amino group yielded the highest conversion rates. Replacing the epsilon-acetyl group with larger lipophilic acyl substituents led to a pronounced decrease in conversion by class I and II enzymes; the class III enzyme displayed a greater tolerance. Incubations with recombinant FLAG-tagged human HDACs 1, 3, and 6 showed a distinct subtype selectivity among small molecule substrates. The subtype selectivity of HDAC inhibitors could be predicted with these substrates and an easily obtainable mixture of HDAC subtypes.

  DOI：

  10.1021/jm0497592

文献信息

• Subtype Selective Substrates for Histone Deacetylases
  作者：Birgit Heltweg、Franck Dequiedt、Brett L. Marshall、Carsten Brauch、Minoru Yoshida、Norikazu Nishino、Eric Verdin、Manfred Jung

  DOI：10.1021/jm0497592

  日期：2004.10.1

  To probe the steric requirements for deacylation, we synthesized lysine-derived small molecule substrates and examined structure -reactivity relationships with various histone deacetylases. Rat liver, human HeLa, and human recombinant class I and II histone deacetylases (HDACs) as well as human recombinant NAD(+)-dependent SIRT1 (class III enzyme) were used in these studies. A benzyloxycarbonyl substituent on the alpha-amino group yielded the highest conversion rates. Replacing the epsilon-acetyl group with larger lipophilic acyl substituents led to a pronounced decrease in conversion by class I and II enzymes; the class III enzyme displayed a greater tolerance. Incubations with recombinant FLAG-tagged human HDACs 1, 3, and 6 showed a distinct subtype selectivity among small molecule substrates. The subtype selectivity of HDAC inhibitors could be predicted with these substrates and an easily obtainable mixture of HDAC subtypes.