1-(cyclohexylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol | 301160-09-8

• 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: 1-(cyclohexylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol
• 英文别名: 1-(Cyclohexylamino)-3-(3,6-dichlorocarbazol-9-yl)propan-2-ol
• CAS: 301160-09-8
• 化学式: C₂₁H₂₄Cl₂N₂O
• 分子量: 391.34
• InChiKey: JAEHRJLXQLQEPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  37.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3,6-二氯咔唑 在 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(cyclohexylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol
  参考文献：
  名称：

  Membrane-Targeting DCAP Analogues with Broad-Spectrum Antibiotic Activity against Pathogenic Bacteria

  摘要：

  We performed a structure activity relationship study of 2-((3-(3,6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl)amino)-2-(hydroxymethyl)propane-1,3-diol (DCAP), which is an antibacterial agent that disrupts the membrane potential and permeability of bacteria. The stereochemistry of DCAP had no effect on the biological activity of DCAP. The aromaticity and electronegativity of the chlorine-substituted carbazole was required for activity, suggesting that its planar and dipolar characteristics orient DCAP in membranes. Increasing the hydrophobicity of the tail region of DCAP enhanced its antibiotic activity. Two DCAP analogues displayed promising antibacterial activity against the BSL-3 pathogens Bacillus anthracis and Francisella tularensis. Codosing DCAP analogues with ampicillin or kanamycin increased their potency. These studies demonstrate that DCAP and its analogues may be a promising scaffold for developing chemotherapeutic agents that bind to bacterial membranes and kill strains of slow-growing or dormant bacteria that cause persistent infections.

  DOI：

  10.1021/acsmedchemlett.5b00024

文献信息

• Antimicrobial compounds, compositions and methods of use thereof
  申请人：Wisconsin Alumni Research Foundation

  公开号：US10314816B2

  公开（公告）日：2019-06-11

  Described herein are antimicrobial compounds identified via a high-throughput inhibitor screen of the in vitro activity of MipZ, which is an ATPase that regulates division site placement in Caulobacter crescentus. The compounds and their analogs are active against bacterial membranes and thus represent a novel class of antimicrobial compounds. The antimicrobial compounds are effective against both actively growing bacterial cells as well as bacterial cells in the stationary phase. The antimicrobial compounds are also effective against bacteria in biofilms.

  本文介绍的抗菌化合物是通过对 MipZ 的体外活性进行高通量抑制剂筛选而发现的，MipZ 是一种 ATP 酶，可调节新月杆菌分裂位点的位置。这些化合物及其类似物对细菌膜具有活性，因此是一类新型抗菌化合物。这些抗菌化合物对活跃生长的细菌细胞和处于静止期的细菌细胞都有效。这些抗菌化合物对生物膜中的细菌也有效。
• Membrane-Targeting DCAP Analogues with Broad-Spectrum Antibiotic Activity against Pathogenic Bacteria
  作者：Katherine A. Hurley、Victoria A. Heinrich、Jeremy R. Hershfield、Samandra T. Demons、Douglas B. Weibel

  DOI：10.1021/acsmedchemlett.5b00024

  日期：2015.4.9

  We performed a structure activity relationship study of 2-((3-(3,6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl)amino)-2-(hydroxymethyl)propane-1,3-diol (DCAP), which is an antibacterial agent that disrupts the membrane potential and permeability of bacteria. The stereochemistry of DCAP had no effect on the biological activity of DCAP. The aromaticity and electronegativity of the chlorine-substituted carbazole was required for activity, suggesting that its planar and dipolar characteristics orient DCAP in membranes. Increasing the hydrophobicity of the tail region of DCAP enhanced its antibiotic activity. Two DCAP analogues displayed promising antibacterial activity against the BSL-3 pathogens Bacillus anthracis and Francisella tularensis. Codosing DCAP analogues with ampicillin or kanamycin increased their potency. These studies demonstrate that DCAP and its analogues may be a promising scaffold for developing chemotherapeutic agents that bind to bacterial membranes and kill strains of slow-growing or dormant bacteria that cause persistent infections.