6-chloro-2,3,4,9-tetrahydro-1H-carbazole-7-carboxylic acid | 676470-14-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-7-carboxylic acid
• 英文别名: 3-chloro-6,7,8,9-tetrahydro-5H-carbazole-2-carboxylic acid
• CAS: 676470-14-7
• 化学式: C₁₃H₁₂ClNO₂
• mdl: MFCD05625691
• 分子量: 249.697
• InChiKey: QPXAEUZWZDSOOF-UHFFFAOYSA-N

物化性质

• 溶解度：
  >37.5 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  甲醇 、 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-7-carboxylic acid 在 硫酸 作用下， 以18%的产率得到methyl 6-chloro-2,3,4,9-tetrahydrocarbazole-7-carboxylate
  参考文献：
  名称：

  Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach

  摘要：

  The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.

  DOI：

  10.1021/jm500122r
• 作为产物：
  描述：

  环己酮 、 2-chloro-5-hydrazinobenzoic acid hydrochloride 在 溶剂黄146 作用下， 以16%的产率得到6-chloro-2,3,4,9-tetrahydro-1H-carbazole-7-carboxylic acid
  参考文献：
  名称：

  Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach

  摘要：

  The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.

  DOI：

  10.1021/jm500122r

文献信息

• Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach
  作者：Zhou Yin、Louise R. Whittell、Yao Wang、Slobodan Jergic、Michael Liu、Elizabeth J. Harry、Nicholas E. Dixon、Jennifer L. Beck、Michael J. Kelso、Aaron J. Oakley

  DOI：10.1021/jm500122r

  日期：2014.3.27

  The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.