(7-azido-1-cyanoheptan-2-yl) N-[4-(diethylcarbamoyl)phenyl]-N-[[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl]oxymethyl]carbamate | 1574389-55-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: (7-azido-1-cyanoheptan-2-yl) N-[4-(diethylcarbamoyl)phenyl]-N-[[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl]oxymethyl]carbamate
• CAS: 1574389-55-1
• 化学式: C₄₃H₄₈N₈O₈
• 分子量: 804.903
• InChiKey: ZXMARYCJFRTNAM-BAHNKCPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  59
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  177
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (7-azido-1-cyanoheptan-2-yl) N-[4-(diethylcarbamoyl)phenyl]-N-[[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl]oxymethyl]carbamate 在 溶剂黄146 、 三甲基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (7-amino-1-cyanoheptan-2-yl) N-[4-(diethylcarbamoyl)phenyl]-N-[[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl]oxymethyl]carbamate
  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
• 作为产物：
  描述：

  4-氨基-N,N-二乙基苯甲酰胺 在 三甲基氯硅烷 、 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 26.5h， 生成 (7-azido-1-cyanoheptan-2-yl) N-[4-(diethylcarbamoyl)phenyl]-N-[[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl]oxymethyl]carbamate
  参考文献：
  名称：

  [EN] SLOW-RELEASE CONJUGATES OF SN-38
  [FR] CONJUGUÉS DE SN -38 À LIBÉRATION LENTE

  摘要：

  描述了提供最佳药物释放速率并最小化相应葡萄糖醛酸盐形成的SN-38的共轭物。这些共轭物通过β-消除机制从聚乙二醇中释放SN-38。

  公开号：

  WO2015051307A1

文献信息

• SLOW-RELEASE CONJUGATES OF SN-38
  申请人：PROLYNX LLC

  公开号：US20160243106A1

  公开（公告）日：2016-08-25

  Conjugates of SN-38 that provide optimal drug release rates and minimize the formation of the corresponding glucuronate are described. The conjugates release SN-38 from a polyethylene glycol through a β-elimination mechanism.

  本文描述了SN-38的共轭物，这些共轭物提供最佳的药物释放速率并最小化相应糖醛酸盐的形成。这些共轭物通过β-消除机制从聚乙二醇中释放SN-38。
• Slow-release conjugates of SN-38
  申请人：ProLynx LLC

  公开号：US10016411B2

  公开（公告）日：2018-07-10

  Conjugates of SN-38 that provide optimal drug release rates and minimize the formation of the corresponding glucuronate are described. The conjugates release SN-38 from a polyethylene glycol through a β-elimination mechanism.

  本文描述了 SN-38 的共轭物，这种共轭物能提供最佳的药物释放率，并能最大程度地减少相应葡萄糖醛酸的形成。这些共轭物通过β-消除机制从聚乙二醇中释放 SN-38。