2-chloro-6-methyl-1H-benzoimidazole-5-carbonitrile | 1388029-46-6

• 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: 2-chloro-6-methyl-1H-benzoimidazole-5-carbonitrile
• 英文别名: 2-chloro-6-methyl-1H-benzimidazole-5-carbonitrile
• CAS: 1388029-46-6
• 化学式: C₉H₆ClN₃
• 分子量: 191.62
• InChiKey: HBYIBGFKLRIYPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  52.47
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  7-methoxy-1-(2-(piperazin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one 、 2-chloro-6-methyl-1H-benzoimidazole-5-carbonitrile 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以26%的产率得到2-(4-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperazin-1-yl)-6-methyl-1H-benzo[d]imidazole-5-carbonitrile
  参考文献：
  名称：

  Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing

  摘要：

  Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chemical series that has been the major challenges for NBTIs.

  DOI：

  10.1021/ml5001728
• 作为产物：
  描述：

  4,5-diamino-2-methyl-benzonitrile 在 盐酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 2-chloro-6-methyl-1H-benzoimidazole-5-carbonitrile
  参考文献：
  名称：

  Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing

  摘要：

  Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chemical series that has been the major challenges for NBTIs.

  DOI：

  10.1021/ml5001728