1,3-dimethyl-5-nitro-6-(piperidin-1-yl)-1H-benzo[d]imidazol-2(3H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1,3-dimethyl-5-nitro-6-(piperidin-1-yl)-1H-benzo[d]imidazol-2(3H)-one
• 英文别名: 1,3-Dimethyl-5-nitro-6-(piperidin-1-YL)-2,3-dihydro-1H-1,3-benzodiazol-2-one；1,3-dimethyl-5-nitro-6-piperidin-1-ylbenzimidazol-2-one
• 化学式: C₁₄H₁₈N₄O₃
• mdl: MFCD00476642
• 分子量: 290.322
• InChiKey: HEIHBTGMQBQOHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3-dimethyl-5-nitro-6-(piperidin-1-yl)-1H-benzo[d]imidazol-2(3H)-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 16.0h， 以99%的产率得到5-amino-1,3-dimethyl-6-(piperidin-1-yl)-1H-benzo[d]imidazol-2(3H)-one
  参考文献：
  名称：

  1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain

  摘要：

  The BRPF (bromodomain and PHD finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. Here, we report the discovery, binding mode, and structureactivity relationship (SAR) of the first potent, selective series of inhibitors of the BRPF1 bromodomain.

  DOI：

  10.1021/ml5002932
• 作为产物：
  描述：

  5-fluoro-1,3-dimethyl-1H-benzo[d]imidazol-2(3H)-one 在 硝酸 、 乙酸酐 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 生成 1,3-dimethyl-5-nitro-6-(piperidin-1-yl)-1H-benzo[d]imidazol-2(3H)-one
  参考文献：
  名称：

  1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain

  摘要：

  The BRPF (bromodomain and PHD finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. Here, we report the discovery, binding mode, and structureactivity relationship (SAR) of the first potent, selective series of inhibitors of the BRPF1 bromodomain.

  DOI：

  10.1021/ml5002932

文献信息

• GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain
  作者：Paul Bamborough、Heather A. Barnett、Isabelle Becher、Mark J. Bird、Chun-wa Chung、Peter D. Craggs、Emmanuel H. Demont、Hawa Diallo、David J. Fallon、Laurie J. Gordon、Paola Grandi、Clare I. Hobbs、Edward Hooper-Greenhill、Emma J. Jones、Robert P. Law、Armelle Le Gall、David Lugo、Anne-Marie Michon、Darren J. Mitchell、Rab K. Prinjha、Robert J. Sheppard、Allan J. B. Watson、Robert J. Watson

  DOI：10.1021/acsmedchemlett.6b00092

  日期：2016.6.9

  The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micro molar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.