11,12-carbonate-11,12-dideoxy-4"-O-(3-aminopropyl)azithromycin | 906453-24-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 11,12-carbonate-11,12-dideoxy-4"-O-(3-aminopropyl)azithromycin
• 英文别名: (1R,2R,5R,6S,7S,8R,9R,11R,14R,15R)-6-[(2R,4R,5S,6S)-5-(3-aminopropoxy)-4-methoxy-4,6-dimethyloxan-2-yl]oxy-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-hydroxy-1,5,7,9,11,13,14-heptamethyl-3,16,18-trioxa-13-azabicyclo[13.3.0]octadecane-4,17-dione
• CAS: 906453-24-5
• 化学式: C₄₂H₇₇N₃O₁₃
• 分子量: 832.086
• InChiKey: QEUGVSCIZGFKNU-ZQKYIICCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  58
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  190
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  11,12-carbonate-11,12-dideoxy-4"-O-(3-aminopropyl)azithromycin 在 水 、 溶剂黄146 、 sodium nitrite 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 3.0h， 以58%的产率得到4''-O-(3-hydroxypropyl)azithromycin 11,12-cyclic carbonate
  参考文献：
  名称：

  Synthesis and properties of macrolones characterized by two ether bonds in the linker

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2010.07.007
• 作为产物：
  描述：

  2'-O-acetyl-azithromycin-11,12-carbonate 在 platinum(IV) oxide 甲醇 、 氢气 、 sodium hydride 、 叔丁醇 作用下， 以 溶剂黄146 为溶剂， 55.0 ℃ 、500.01 kPa 条件下， 反应 24.0h， 生成 11,12-carbonate-11,12-dideoxy-4"-O-(3-aminopropyl)azithromycin
  参考文献：
  名称：

  Macrolides With Anti-Inflammatory Activity

  摘要：

  本发明涉及具有抗炎活性的新型半合成大环内酯类化合物。更具体地说，该发明涉及在4″位置取代的14-和15-环大环内酯类化合物，及其药学上可接受的衍生物，用于其制备的工艺和中间体，含有它们的制剂，以及它们在治疗人类和动物的炎症性疾病和症状中的活性和用途，特别是那些与过度分泌TNF-α、IL-1、IL-8、IL-2或IL-5有关的疾病；和/或抑制过度淋巴细胞增殖；和/或过度粒细胞脱颗粒的抑制剂。

  公开号：

  US20080221046A1

文献信息

• Macrolides with Anti-Inflammatory Activity
  申请人：Alihodzic Sulejman

  公开号：US20120058963A1

  公开（公告）日：2012-03-08

  The present invention relates to novel semi-synthetic macrolides having anti-inflammatory activity. More particularly, the invention relates to 14- and 15-membered macrolides substituted at the 4″ position, to their pharmaceutically acceptable derivatives, to processes and intermediates for their preparation, to pharmaceutical compositions containing them and to their activity and use in the treatment of inflammatory diseases and conditions in humans and animals, especially those diseases associated with excessive secretion of TNF-α, IL-1, IL-8, IL-2 or IL-5; and/or inhibitor of excessive lymphocyte proliferation; and/or excessive granulocyte degranulation.
• US8080529B2
  申请人：——

  公开号：US8080529B2

  公开（公告）日：2011-12-20
• 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.
• Macrolides With Anti-Inflammatory Activity
  申请人：Culic Ognjen

  公开号：US20080221046A1

  公开（公告）日：2008-09-11

  The present invention relates to novel semi-synthetic macrolides having anti-inflammatory activity. More particularly, the invention relates to 14- and 15-membered macrolides substituted at the 4″ position, to their pharmaceutically acceptable derivatives, to processes and intermediates for their preparation, to pharmaceutical compositions containing them and to their activity and use in the treatment of inflammatory diseases and conditions in humans and animals, especially those diseases associated with excessive secretion of TNF-α, IL-1, IL-8, IL-2 or IL-5; and/or inhibitor of excessive lymphocyte proliferation; and/or excessive granulocyte degranulation.

  本发明涉及具有抗炎活性的新型半合成大环内酯类化合物。更具体地说，该发明涉及在4″位置取代的14-和15-环大环内酯类化合物，及其药学上可接受的衍生物，用于其制备的工艺和中间体，含有它们的制剂，以及它们在治疗人类和动物的炎症性疾病和症状中的活性和用途，特别是那些与过度分泌TNF-α、IL-1、IL-8、IL-2或IL-5有关的疾病；和/或抑制过度淋巴细胞增殖；和/或过度粒细胞脱颗粒的抑制剂。