5-nitro-1,3-dihydro-2H-naphtho[1,2-d]imidazol-2-one | 144366-25-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-nitro-1,3-dihydro-2H-naphtho[1,2-d]imidazol-2-one
• 英文别名: 5-Nitro-1,3-dihydrobenzo[e]benzimidazol-2-one
• CAS: 144366-25-6
• 化学式: C₁₁H₇N₃O₃
• 分子量: 229.195
• InChiKey: UCKXVBCLLDGSTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-氯-2-硝基-1-萘胺 在 palladium 10% on activated carbon 、 氢气 、 硝酸 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 50.0 ℃ 、300.01 kPa 条件下， 反应 14.5h， 生成 5-nitro-1,3-dihydro-2H-naphtho[1,2-d]imidazol-2-one
  参考文献：
  名称：

  Synthesis and biological activity of splitomicin analogs targeted at human NAD+-dependent histone deacetylases (sirtuins)

  摘要：

  Small molecules interfering with posttranslational modification of histones are of interest as tools to study epigenetic regulation of gene transcription. Specifically, drugs that interfere with histone deacetylation could be useful to induce differentiation, growth arrest as well as apoptotic cell death in tumor cells. One class of histone deacetylases is known as sirtuins some of which (Saccharomyces cerevisiae Sir2) are for example inhibited by the lactone splitomicin leading to telomeric silencing in yeast. However, splitomicin is only a micromolar inhibitor of yeast Sir2 and does not inhibit human subtypes and the lactone is prone to hydrolytic ring opening. In preliminary SAR-studies, splitomicin analogs lacking this hydrolytically labile ring were described as inactive while the naphthalene moiety could successfully be replaced by smaller aromatic rings in a fragment-like dihydrocoumarin. Here we report the synthesis and biological activity of a series of hydrolytically stable analogs with activity against human SIRT1 and 2. These comparatively small compounds characterized by high ligand efficiency are used as a starting point toward the development of specific inhibitors of histone deacetylases from the class of sirtuins. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.026

文献信息

• Synthesis and biological activity of splitomicin analogs targeted at human NAD+-dependent histone deacetylases (sirtuins)
  作者：Marcus Freitag、Jörg Schemies、Tim Larsen、Khattab El Gaghlab、Felix Schulz、Tobias Rumpf、Manfred Jung、Andreas Link

  DOI：10.1016/j.bmc.2011.01.026

  日期：2011.6

  Small molecules interfering with posttranslational modification of histones are of interest as tools to study epigenetic regulation of gene transcription. Specifically, drugs that interfere with histone deacetylation could be useful to induce differentiation, growth arrest as well as apoptotic cell death in tumor cells. One class of histone deacetylases is known as sirtuins some of which (Saccharomyces cerevisiae Sir2) are for example inhibited by the lactone splitomicin leading to telomeric silencing in yeast. However, splitomicin is only a micromolar inhibitor of yeast Sir2 and does not inhibit human subtypes and the lactone is prone to hydrolytic ring opening. In preliminary SAR-studies, splitomicin analogs lacking this hydrolytically labile ring were described as inactive while the naphthalene moiety could successfully be replaced by smaller aromatic rings in a fragment-like dihydrocoumarin. Here we report the synthesis and biological activity of a series of hydrolytically stable analogs with activity against human SIRT1 and 2. These comparatively small compounds characterized by high ligand efficiency are used as a starting point toward the development of specific inhibitors of histone deacetylases from the class of sirtuins. (C) 2011 Elsevier Ltd. All rights reserved.