| 1251900-25-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 1251900-25-0
• 化学式: C₄₂H₇₄N₂O₁₃
• 分子量: 815.055
• InChiKey: AVLYKLMLHIXKEA-ZQKYIICCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  57.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  164.15
• 氢给体数：
  2.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  在 甲醇 、 sodium periodate 、 四氧化锇 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 6.0h， 生成 4"-(3-carboxy-propoxy)-azithromycin
  参考文献：
  名称：

  Discovery of 4′′-Ether Linked Azithromycin-Quinolone Hybrid Series: Influence of the Central Linker on the Antibacterial Activity

  摘要：

  A series of novel C-4"-substituted azithromycins was synthesized and evaluated for in vitro antibacterial activity against a panel of representative erythromycin-susceptible and macrolide-lincosamide-streptogramin (MLS) resistant pathogens. In summary, azithromycin and quinolone substructures merged in a mutually SAR-compatible design gave rise to a new class of antimicrobials with an improved spectrum and potency over azithromycin. Prototypical analogues 71 and, 8f display an improved potency versus azithromycin against Gram-positive and fastidious Gram-negative pathogens. In particular, these new leads maintain activity against MLS-resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes. In addition, they represent an improvement over telithromycin (1) and cethromycin (2) against the fastidious Gram-negative pathogen Haemophilus influenzae.

  DOI：

  10.1021/ml100253p
• 作为产物：
  描述：

  2'-O-acetyl-4''-O-allyl-azithromycin-11,12-carbonate 在 甲醇 作用下， 反应 20.0h， 生成
  参考文献：
  名称：

  Discovery of 4′′-Ether Linked Azithromycin-Quinolone Hybrid Series: Influence of the Central Linker on the Antibacterial Activity

  摘要：

  A series of novel C-4"-substituted azithromycins was synthesized and evaluated for in vitro antibacterial activity against a panel of representative erythromycin-susceptible and macrolide-lincosamide-streptogramin (MLS) resistant pathogens. In summary, azithromycin and quinolone substructures merged in a mutually SAR-compatible design gave rise to a new class of antimicrobials with an improved spectrum and potency over azithromycin. Prototypical analogues 71 and, 8f display an improved potency versus azithromycin against Gram-positive and fastidious Gram-negative pathogens. In particular, these new leads maintain activity against MLS-resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes. In addition, they represent an improvement over telithromycin (1) and cethromycin (2) against the fastidious Gram-negative pathogen Haemophilus influenzae.

  DOI：

  10.1021/ml100253p

文献信息

• Synthesis and properties of macrolones characterized by two ether bonds in the linker
  作者：Ivana Palej Jakopović、Goran Kragol、Andrew K. Forrest、Catherine S.V. Frydrych、Vlado Štimac、Samra Kapić、Maja Matanović Škugor、Marina Ilijaš、Hana Čipčić Paljetak、Dubravko Jelić、David J. Holmes、Deirdre M.B. Hickey、Donatella Verbanac、Vesna Eraković Haber、Sulejman Alihodžić

  DOI：10.1016/j.bmc.2010.07.007

  日期：2010.9

  In this paper synthesis of macrolones 1-18 starting from azithromycin is reported. Two key steps in the construction of the linker between macrolide and quinolone moiety, are formation of central ether bond by alkylation of unactivated OH group, and formation of terminal C-C bond at 6-position of the quinolone unit. Due to the difficulty in formation of these two bonds the study of alternative synthetic methodologies and optimization of the conditions for the selected routes was required. Formation of C-4"-O-ether bond was completed by modified Michael addition, whereas O-alkylation via diazonium cation proved to be the most effective in formation of the central allylic or propargylic ether bond. Comparison of Heck and Sonogashira reaction revealed the former as preferred route to the C-C bond formation at C(6) position of the quinolone unit. Most of the target compounds exhibited highly favorable antibacterial activity against common respiratory pathogens, without significant cytotoxicity profile when tested in vitro on eukaryotic cell lines. (C) 2010 Elsevier Ltd. All rights reserved.