| 1574389-58-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• CAS: 1574389-58-4
• 化学式: C₄₁H₄₉N₅O₈
• 分子量: 739.869
• InChiKey: OSGAAXZDWCYHSN-RWYGWLOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.62
• 重原子数：
  54.0
• 可旋转键数：
  15.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  166.52
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  4-氨基-N,N-二乙基苯甲酰胺 在 吡啶 、 三甲基氯硅烷 、 potassium tert-butylate 、 溶剂黄146 、 三乙胺 、 三甲基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 28.25h， 生成
  参考文献：
  名称：

  Macromolecular Prodrug That Provides the Irinotecan (CPT-11) Active-Metabolite SN-38 with Ultralong Half-Life, Low C_max , and Low Glucuronide Formation

  摘要：

  We have recently reported a chemical approach for half-life extension that utilizes β-eliminative linkers to attach amine-containing drugs or prodrugs to macromolecules. The linkers release free drug or prodrug over periods ranging from a few hours to over 1 year. We adapted these linkers for use with phenol-containing drugs. Here, we prepared PEG conjugates of the irinotecan (CPT-11) active metabolite SN-38 via a phenyl ether that release the drug with predictable long half-lives. Pharmacokinetic studies in the rat indicate that, in contrast to other SN-38 prodrugs, the slowly released SN-38 shows a very low C(max), is kept above target concentrations for extended periods, and forms very little SN-38 glucuronide (the precursor of enterotoxic SN-38). The low SN-38 glucuronide is attributed to low hepatic uptake of SN-38. These macromolecular prodrugs have unique pharmacokinetic profiles that may translate to less intestinal toxicity and interpatient variability than the SN-38 prodrugs thus far studied.

  DOI：

  10.1021/jm401644v