(R)-9-(2-((4-(2-amino-2-oxoethyl)phenyl)amino)-2-oxoethyl)-6-chloro-2,3,4,9-tetrahydro-1Hcarbazole-2-carboxylic acid

• 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: (R)-9-(2-((4-(2-amino-2-oxoethyl)phenyl)amino)-2-oxoethyl)-6-chloro-2,3,4,9-tetrahydro-1Hcarbazole-2-carboxylic acid
• 英文别名: (2R)-9-[2-[4-(2-amino-2-oxoethyl)anilino]-2-oxoethyl]-6-chloro-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid
• 化学式: C₂₃H₂₂ClN₃O₄
• 分子量: 439.898
• InChiKey: AKHYHZLJFYSVFO-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-3-oxocyclohexanecarboxylic acid 在 硫酸 、 caesium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 (R)-9-(2-((4-(2-amino-2-oxoethyl)phenyl)amino)-2-oxoethyl)-6-chloro-2,3,4,9-tetrahydro-1Hcarbazole-2-carboxylic acid
  参考文献：
  名称：

  Bacterial Sliding Clamp Inhibitors that Mimic the Sequential Binding Mechanism of Endogenous Linear Motifs

  摘要：

  The bacterial DNA replication machinery presents new targets for the development of antibiotics acting via novel mechanisms. One such target is the protein-protein interaction between the DNA sliding clamp and the conserved peptide linear motifs in DNA polymerases. We previously established that binding of linear motifs to the Escherichia coli sliding clamp occurs via a sequential mechanism that involves two subsites (I and II). Here, we report the development of small-molecule inhibitors that mimic this mechanism. The compounds contain tetrahydrocarbazole moieties as "anchors" to occupy subsite I. Functional groups appended at the tetrahydrocarbazole nitrogen bind to a channel gated by the side chain of M362 and lie at the edge of subsite II. One derivative induced the formation of a new binding pocket, termed subsite III, by rearrangement of a loop adjacent to subsite I. Discovery of the extended binding area will guide further inhibitor development.

  DOI：

  10.1021/acs.jmedchem.5b00232

文献信息

• Bacterial Sliding Clamp Inhibitors that Mimic the Sequential Binding Mechanism of Endogenous Linear Motifs
  作者：Zhou Yin、Louise R. Whittell、Yao Wang、Slobodan Jergic、Cong Ma、Peter J. Lewis、Nicholas E. Dixon、Jennifer L. Beck、Michael J. Kelso、Aaron J. Oakley

  DOI：10.1021/acs.jmedchem.5b00232

  日期：2015.6.11

  The bacterial DNA replication machinery presents new targets for the development of antibiotics acting via novel mechanisms. One such target is the protein-protein interaction between the DNA sliding clamp and the conserved peptide linear motifs in DNA polymerases. We previously established that binding of linear motifs to the Escherichia coli sliding clamp occurs via a sequential mechanism that involves two subsites (I and II). Here, we report the development of small-molecule inhibitors that mimic this mechanism. The compounds contain tetrahydrocarbazole moieties as "anchors" to occupy subsite I. Functional groups appended at the tetrahydrocarbazole nitrogen bind to a channel gated by the side chain of M362 and lie at the edge of subsite II. One derivative induced the formation of a new binding pocket, termed subsite III, by rearrangement of a loop adjacent to subsite I. Discovery of the extended binding area will guide further inhibitor development.