6-[3-(4-ethoxycarbonyl-butoxy)-propyn-1-yl]-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester | 1248571-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-[3-(4-ethoxycarbonyl-butoxy)-propyn-1-yl]-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 6-[3-(5-ethoxy-5-oxopentoxy)prop-1-ynyl]-1-ethyl-4-oxoquinoline-3-carboxylate
• CAS: 1248571-04-1
• 化学式: C₂₄H₂₉NO₆
• 分子量: 427.497
• InChiKey: RXMWBOVBWYLZEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-[3-(4-ethoxycarbonyl-butoxy)-propyn-1-yl]-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 14.0h， 以185 mg的产率得到6-[3-(4-carboxy-butoxy)-propyn-1-yl]-1-ethyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  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
• 作为产物：
  描述：

  ethyl 1-ethyl-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate 、 ethyl 5-(prop-2-yn-1-yloxy)pentanoate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 乙腈 为溶剂， 以0.48 g的产率得到6-[3-(4-ethoxycarbonyl-butoxy)-propyn-1-yl]-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
  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.