(4R)-N-[2-[[2-[[[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino]methyl]-1,3-benzothiazol-5-yl]oxy]ethyl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-thiazole-4-carboxamide | 1426097-05-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4R)-N-[2-[[2-[[[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino]methyl]-1,3-benzothiazol-5-yl]oxy]ethyl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-thiazole-4-carboxamide
• CAS: 1426097-05-3
• 化学式: C₂₉H₂₃Cl₂N₇O₃S₂
• 分子量: 652.585
• InChiKey: SFZDSEJQTLDXSF-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  188
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  、 dihydroaeruginoic acid 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以30%的产率得到(4R)-N-[2-[[2-[[[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino]methyl]-1,3-benzothiazol-5-yl]oxy]ethyl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Vectorization Efforts To Increase Gram-Negative Intracellular Drug Concentration: A Case Study on HldE-K Inhibitors

  摘要：

  In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their Gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.

  DOI：

  10.1021/jm400097h

文献信息

• Vectorization Efforts To Increase Gram-Negative Intracellular Drug Concentration: A Case Study on HldE-K Inhibitors
  作者：Dmytro Atamanyuk、Fabien Faivre、Mayalen Oxoby、Benoit Ledoussal、Elodie Drocourt、François Moreau、Vincent Gerusz

  DOI：10.1021/jm400097h

  日期：2013.3.14

  In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their Gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.