4''-O-{5-[3-(3-carboxy-1-ethyl-4-oxo-1,4-dihydro-quinolin-6-yl)-propoxy]-pentanoyloxy}-azithromycin | 1248571-07-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4''-O-{5-[3-(3-carboxy-1-ethyl-4-oxo-1,4-dihydro-quinolin-6-yl)-propoxy]-pentanoyloxy}-azithromycin
• 英文别名: 6-[3-[5-[(2S,3S,4R,6R)-6-[[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-1-oxa-6-azacyclopentadec-13-yl]oxy]-4-methoxy-2,4-dimethyloxan-3-yl]oxy-5-oxopentoxy]propyl]-1-ethyl-4-oxoquinoline-3-carboxylic acid
• CAS: 1248571-07-4
• 化学式: C₅₈H₉₅N₃O₁₇
• 分子量: 1106.4
• InChiKey: XZMBDEKSGXJBNJ-JIDZQRHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  78
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  253
• 氢给体数：
  5
• 氢受体数：
  20

反应信息

• 作为产物：
  描述：

  6-[3-[5-[(2S,3S,4R,6R)-6-[[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-1-oxa-6-azacyclopentadec-13-yl]oxy]-4-methoxy-2,4-dimethyloxan-3-yl]oxy-5-oxopentoxy]prop-1-ynyl]-1-ethyl-4-oxoquinoline-3-carboxylic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 20.0h， 以2.08 mg的产率得到4''-O-{5-[3-(3-carboxy-1-ethyl-4-oxo-1,4-dihydro-quinolin-6-yl)-propoxy]-pentanoyloxy}-azithromycin
  参考文献：
  名称：

  6-Alkylquinolone-3-carboxylic acid tethered to macrolides synthesis and antimicrobial profile

  摘要：

  Two series of clarithromycin and azithromycin derivatives with terminal 6-alkylquinolone-3-carboxylic unit with central ether bond in the linker were prepared and tested for antimicrobial activity. Quinolonelinker intermediates were prepared by Sonogashira-type C(6)-alkynylation of 6-iodo-quinolone precursors. In the last step, 400 site-selective acylation of 2'-protected macrolides was completed with the EDC reagent, which selectively activated a terminal, aliphatic carboxylic group in dicarboxylic intermediates. Antimicrobial activity of the new series of macrolones is discussed. The most potent compound, 4"-O-{6-[3-(3-carboxy-1-ethyl-4-oxo-1,4-dihydroquinolin-6-yl)-propoxy]-hexanoyl}-azithromycin (10), is highly active against bacterial respiratory pathogens resistant to macrolide antibiotics and represents a promising lead for further investigation. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.048

文献信息

• 6-Alkylquinolone-3-carboxylic acid tethered to macrolides synthesis and antimicrobial profile
  作者：Samra Kapić、Hana Čipčić Paljetak、Sulejman Alihodžić、Roberto Antolović、Vesna Eraković Haber、Richard L. Jarvest、David J. Holmes、John P. Broskey、Eric Hunt

  DOI：10.1016/j.bmc.2010.06.048

  日期：2010.9

  Two series of clarithromycin and azithromycin derivatives with terminal 6-alkylquinolone-3-carboxylic unit with central ether bond in the linker were prepared and tested for antimicrobial activity. Quinolonelinker intermediates were prepared by Sonogashira-type C(6)-alkynylation of 6-iodo-quinolone precursors. In the last step, 400 site-selective acylation of 2'-protected macrolides was completed with the EDC reagent, which selectively activated a terminal, aliphatic carboxylic group in dicarboxylic intermediates. Antimicrobial activity of the new series of macrolones is discussed. The most potent compound, 4"-O-6-[3-(3-carboxy-1-ethyl-4-oxo-1,4-dihydroquinolin-6-yl)-propoxy]-hexanoyl}-azithromycin (10), is highly active against bacterial respiratory pathogens resistant to macrolide antibiotics and represents a promising lead for further investigation. (C) 2010 Elsevier Ltd. All rights reserved.