(1S,2R,5Z,7S,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadec-5-ene-4,12,16-trione

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,2R,5Z,7S,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadec-5-ene-4,12,16-trione
• 化学式: C₄₃H₆₅N₅O₉
• 分子量: 796.017
• InChiKey: IKKCSESMCDMXSQ-CANHLPCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  57
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  155
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  Imidazole-1-carboxylic acid (4E,12Z)-(2R,3S,7R,9R,10R,11S)-10-((2S,3R,4S,6R)-3-acetoxy-4-dimethylamino-6-methyl-tetrahydro-pyran-2-yloxy)-2-ethyl-9-methoxy-3,5,7,9,11,13-hexamethyl-6,14-dioxo-oxacyclotetradeca-4,12-dien-3-yl ester 在 甲醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (1S,2R,5Z,7S,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadec-5-ene-4,12,16-trione
  参考文献：
  名称：

  β-Keto-ester chemistry and ketolides. synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides

  摘要：

  The effect of 2,3 modifications on the antibacterial activity of ketolides was evaluated by introducing substituents in position 2 and converting the C-1, C-2, C-3 beta-keto-ester into stable 2,3 enol-ether or 2,3 anhydro derivatives. Introduction of a fluorine in C-2. is beneficial with regard to the overall antibacterial spectrum whereas the enol-ether and 2,3 unsaturated compounds, as well as the bulky gem dimethyl or 2-chloro derivatives, are less active particularly against erythromycin resistant strains. A 2-fluoro ketolide derivative demonstrates good antibacterial activity and in vivo efficacy against multi-resistant Streptococcus pneumoniae. Compared to azithromycin against Haemophilus influenzae, this compound is equivalent in vitro and slightly more active in vivo. These results demonstrate that within the ketolide class, to retain good antibacterial activity, position needs to remain tetrahedral and tolerates only very small substituents such as fluorine. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00392-9

文献信息

• β-Keto-ester chemistry and ketolides. synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides
  作者：Alexis Denis、François Bretin、Claude Fromentin、A Bonnet、Alain Bonnefoy、Constantin Agouridas、G Piltan

  DOI：10.1016/s0960-894x(00)00392-9

  日期：2000.9

  The effect of 2,3 modifications on the antibacterial activity of ketolides was evaluated by introducing substituents in position 2 and converting the C-1, C-2, C-3 beta-keto-ester into stable 2,3 enol-ether or 2,3 anhydro derivatives. Introduction of a fluorine in C-2. is beneficial with regard to the overall antibacterial spectrum whereas the enol-ether and 2,3 unsaturated compounds, as well as the bulky gem dimethyl or 2-chloro derivatives, are less active particularly against erythromycin resistant strains. A 2-fluoro ketolide derivative demonstrates good antibacterial activity and in vivo efficacy against multi-resistant Streptococcus pneumoniae. Compared to azithromycin against Haemophilus influenzae, this compound is equivalent in vitro and slightly more active in vivo. These results demonstrate that within the ketolide class, to retain good antibacterial activity, position needs to remain tetrahedral and tolerates only very small substituents such as fluorine. (C) 2000 Elsevier Science Ltd. All rights reserved.