(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-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecan-15-one | 1383611-53-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮
• 英文名称: (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-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecan-15-one
• CAS: 1383611-53-7
• 化学式: C₄₁H₇₅N₃O₁₂
• 分子量: 802.059
• InChiKey: WNLFYCRAHILCHE-HPIKYMRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  56
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  179
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (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-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecan-15-one 在 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 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：

  N′-Substituted-2′-O,3′-N-carbonimidoyl Bridged Macrolides: Novel Anti-inflammatory Macrolides without Antimicrobial Activity

  摘要：

  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.

  DOI：

  10.1021/jm300356u