2'-O,3'-N-(carbonimidoyl)-3'-N-demethyl-N'-isopropyl-9-deoxo-9a-aza-9a-(2-propyn-1-yl)-9a-homoerythromycin A | 1192304-65-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: 2'-O,3'-N-(carbonimidoyl)-3'-N-demethyl-N'-isopropyl-9-deoxo-9a-aza-9a-(2-propyn-1-yl)-9a-homoerythromycin A
• 英文别名: (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[(3aR,4S,6R,7aS)-1,6-dimethyl-2-propan-2-ylimino-4,6,7,7a-tetrahydro-3aH-pyrano[4,3-d][1,3]oxazol-4-yl]oxy]-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,8,10,12,14-hexamethyl-6-prop-2-ynyl-1-oxa-6-azacyclopentadecan-15-one
• CAS: 1192304-65-6
• 化学式: C₄₃H₇₅N₃O₁₂
• 分子量: 826.081
• InChiKey: WHZPVEQMPJAZHF-PMXZFNMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  58
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  181
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  2'-O,3'-N-(carbonimidoyl)-3'-N-demethyl-N'-isopropyl-9-deoxo-9a-aza-9a-(2-propyn-1-yl)-9a-homoerythromycin A 在 5%-palladium/activated carbon 氢气 作用下， 以 乙醇 为溶剂， 反应 0.67h， 生成 2'-O,3'-N-(carbonimidoyl)-3'-N-demethyl-N'-isopropyl-9-deoxo-9a-aza-9a-propyl-9a-homoerythromycin A
  参考文献：
  名称：

  [EN] 2'-O,3'-N-BRIDGED MACROLIDES
  [FR] MACROLIDES 2'-O,3'-N-PONTÉS

  摘要：

  ' -O, 3 ' -/V-bridged macrolides useful in treatment of inflammatory diseases. More particularly, the invention relates to 2 ' -O, 3 ' -/V-bridged 14- membered macrolides and to 2 ' - O, 3 ' -/V-bridged 15-membered azalide macrolides useful in treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof.

  公开号：

  WO2009130189A1
• 作为产物：
  描述：

  阿奇霉素 A 在 碘 、 N,N-二异丙基乙胺 、 三羟甲基氨基甲烷 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.75h， 生成 2'-O,3'-N-(carbonimidoyl)-3'-N-demethyl-N'-isopropyl-9-deoxo-9a-aza-9a-(2-propyn-1-yl)-9a-homoerythromycin A
  参考文献：
  名称：

  [EN] 2'-O,3'-N-BRIDGED MACROLIDES
  [FR] MACROLIDES 2'-O,3'-N-PONTÉS

  摘要：

  ' -O, 3 ' -/V-bridged macrolides useful in treatment of inflammatory diseases. More particularly, the invention relates to 2 ' -O, 3 ' -/V-bridged 14- membered macrolides and to 2 ' - O, 3 ' -/V-bridged 15-membered azalide macrolides useful in treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof.

  公开号：

  WO2009130189A1

文献信息

• 2'-O,3'-N-BRIDGED MACROLIDES
  申请人：Bukvic-Krajacic Mirjana

  公开号：US20110039795A1

  公开（公告）日：2011-02-17

  Novel 2′-O,3′-N-bridged macrolides useful in treatment of inflammatory diseases. More particularly, the invention relates to 2′-O,3′-N-bridged 14-membered macrolides and to 2′-O,3′-N-bridged 15-membered azalide macrolides useful in treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof.
• [EN] 2'-O,3'-N-BRIDGED MACROLIDES<br/>[FR] MACROLIDES 2'-O,3'-N-PONTÉS
  申请人：GLAXOSMITHKLINE ZAGREB

  公开号：WO2009130189A1

  公开（公告）日：2009-10-29

  Novel 2 ' -O, 3 ' -/V-bridged macrolides useful in treatment of inflammatory diseases. More particularly, the invention relates to 2 ' -O, 3 ' -/V-bridged 14- membered macrolides and to 2 ' - O, 3 ' -/V-bridged 15-membered azalide macrolides useful in treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof.

  ' -O, 3 ' -/V-bridged macrolides useful in treatment of inflammatory diseases. More particularly, the invention relates to 2 ' -O, 3 ' -/V-bridged 14- membered macrolides and to 2 ' - O, 3 ' -/V-bridged 15-membered azalide macrolides useful in treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof.
• <i>N</i>′-Substituted-2′-<i>O</i>,3′-<i>N</i>-carbonimidoyl Bridged Macrolides: Novel Anti-inflammatory Macrolides without Antimicrobial Activity
  作者：Martina Bosnar、Goran Kragol、Sanja Koštrun、Ines Vujasinović、Berislav Bošnjak、Vlatka Bencetić Mihaljević、Zorica Marušić Ištuk、Samra Kapić、Boška Hrvačić、Karmen Brajša、Branka Tavčar、Dubravko Jelić、Ines Glojnarić、Donatella Verbanac、Ognjen Čulić、Jasna Padovan、Sulejman Alihodžić、Vesna Eraković Haber、Radan Spaventi

  DOI：10.1021/jm300356u

  日期：2012.7.12

  Macrolide antibiotics, like erythromycin, clarithromycin, and azithromycin, possess anti-inflammatory properties. These properties are considered fundamental to the efficacy of these three macrolides in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, long-term treatment with macrolide antibiotics presents a considerable risk for promotion of bacterial resistance. We have examined antibacterial and anti-inflammatory effects of a novel macrolide class: N'-substituted 2'-O,3'-N-carbonimidoyl bridged erythromycin-derived 14- and 15-membered macrolides. A small focused library was prepared, and compounds without antimicrobial activity, which inhibited IL-6 production, were selected. Data analysis led to a statistical model that could be used for the design of novel anti-inflammatory macrolides. The most promising compound from this library retained the anti-inflammatory activity observed with azithromycin in lipopolysaccharide-induced pulmonary neutrophilia in vivo. Importantly, this study strongly suggests that antimicrobial and anti-inflammatory activities of macrolides are independent and can be separated, which raises development plausibility of novel anti-inflammatory therapeutics.