N-[[1-[[(2R,3S,4S,5R,6R)-4-amino-6-[(1S,2R,3R,4S,6R)-4,6-diamino-3-[(2R,3R,4S,5S,6R)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-3,5-dihydroxyoxan-2-yl]methyl]triazol-4-yl]methyl]-2-[[2-[[[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino]methyl]-1,3-benzothiazol-5-yl]oxy]acetamide | 1426097-06-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[[1-[[(2R,3S,4S,5R,6R)-4-amino-6-[(1S,2R,3R,4S,6R)-4,6-diamino-3-[(2R,3R,4S,5S,6R)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-3,5-dihydroxyoxan-2-yl]methyl]triazol-4-yl]methyl]-2-[[2-[[[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino]methyl]-1,3-benzothiazol-5-yl]oxy]acetamide
• CAS: 1426097-06-4
• 化学式: C₄₀H₅₁Cl₂N₁₃O₁₂S
• 分子量: 1008.9
• InChiKey: QNDUKFPYTHQWQZ-MRVUHWHESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  68
• 可旋转键数：
  16
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  423
• 氢给体数：
  12
• 氢受体数：
  24

反应信息

• 作为产物：
  描述：

  N,N'-[(1R,3S,4R,5R,6S)-4-({6-deoxy-6-[(2,2-dimethylpropanoyl)amino]-α-D-glucopyranosyl}oxy)-6-({3,6-dideoxy-6-(4-{[({[2-({[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]-amino}methyl)-1,3-benzothiazol-5-yl]oxy}acetyl)amino]-methyl}-1H-1,2,3-triazol-1-yl)-3-[(2,2-dimethylpropanoyl)-amino]-α-D-glucopyranosyl}oxy)-5-hydroxycyclohexane-1,3-diyl]bis(2,2-dimethylpropanamide) 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以64%的产率得到N-[[1-[[(2R,3S,4S,5R,6R)-4-amino-6-[(1S,2R,3R,4S,6R)-4,6-diamino-3-[(2R,3R,4S,5S,6R)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-3,5-dihydroxyoxan-2-yl]methyl]triazol-4-yl]methyl]-2-[[2-[[[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino]methyl]-1,3-benzothiazol-5-yl]oxy]acetamide
  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