splenocin J | 1148106-25-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: splenocin J
• 英文别名: N-[(2R,3S,6S,7R,8R)-8-benzyl-7-hydroxy-2,6-dimethyl-4,9-dioxo-1,5-dioxonan-3-yl]-3-formamido-2-hydroxybenzamide
• CAS: 1148106-25-5
• 化学式: C₂₄H₂₆N₂O₈
• 分子量: 470.479
• InChiKey: JWALONHVQNKYEL-FQUQYDMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  151
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  splenocin J 、 (R)-methoxytrifluoromethylphenylacetyl chloride 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 生成 N-[(2R,3S,6S,7R,8R)-8-benzyl-7-hydroxy-2,6-dimethyl-4,9-dioxo-1,5-dioxonan-3-yl]-2-hydroxy-3-[[(2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl]amino]benzamide
  参考文献：
  名称：

  Potent Inhibitors of Pro-Inflammatory Cytokine Production Produced by a Marine-Derived Bacterium

  摘要：

  Cytokines produced through the antigen presenting cell (APC)-T-cell interaction play a key role in the activation of the allergic asthmatic response. Evaluating small molecules that inhibit the production of these pro-inflammatory proteins is therefore important for the discovery of novel chemical structures with potential antiasthma activity. We adapted a mouse splerrocyte cytokine assay to screen a library of 2,500 marine microbial extracts for their ability to inhibit T(H)2 cytokine release and identified potent activity in a marine-derived strain CNQ431, identified as a Streptomyces species. Bioactivity guided fractionation of the organic extract of this strain led to the isolation of ten new 9-membered bis-lactones, splenocins A-J (1-10). The new compounds display potent biological activities, comparable to that of the corticosteroid dexamethasone, with IC50 values from 2 to 50 nM in the splenocyte cytokine assay. This study provides the foundation for the optimization of these potent anti-inflammatory compounds for development in the treatment of asthma.

  DOI：

  10.1021/jm801110j