1-(4-morpholinosulfonyl)-7-azido-2-heptyl chloroformate | 1346434-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 1-(4-morpholinosulfonyl)-7-azido-2-heptyl chloroformate
• 英文别名: (7-Azido-1-morpholin-4-ylsulfonylheptan-2-yl) carbonochloridate
• CAS: 1346434-40-9
• 化学式: C₁₂H₂₁ClN₄O₅S
• 分子量: 368.842
• InChiKey: KGTPYDIBRWTWKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  95.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(4-morpholinosulfonyl)-7-azido-2-heptyl chloroformate 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
• 作为产物：
  描述：

  三光气 、 1-(morpholinosulfonyl)-7-azido-2-heptanol 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 1-(4-morpholinosulfonyl)-7-azido-2-heptyl chloroformate
  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

文献信息

• [EN] CONTROLLED DRUG RELEASE FROM SOLID SUPPORTS<br/>[FR] SUPPORTS SOLIDES POUR LA LIBÉRATION CONTRÔLÉE DE MÉDICAMENTS
  申请人：PROLYNX LLC

  公开号：WO2011140392A1

  公开（公告）日：2011-11-10

  The invention relates to solid supports useful in medical applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the solid support through a linkage that releases the drug or a prodrug through controlled beta elimination.

  这项发明涉及在医疗应用中有用的固体支持物，可提供药物的控制释放，如肽、核酸和小分子。这些药物通过一个通过受控β消除释放药物或前药的连接与固体支持物共价偶联。
• [EN] CONTROLLED RELEASE FROM MACROMOLECULAR CONJUGATES<br/>[FR] LIBÉRATION CONTRÔLÉE À PARTIR DE CONJUGUÉS MACROMOLÉCULAIRES
  申请人：PROLYNX LLC

  公开号：WO2011140393A1

  公开（公告）日：2011-11-10

  The invention relates to conjugates of macromolecular carriers and drugs comprising linkers that release the drug or a prodrug through rate-controlled beta-elimination, and methods of making and using the conjugates.

  这项发明涉及大分子载体和药物的共轭物，包括释放药物或前药的连接剂，通过速率控制的β-消除释放药物，以及制备和使用这些共轭物的方法。
• CONTROLLED RELEASE FROM MACROMOLECULAR CONJUGATES
  申请人：Ashley Gary

  公开号：US20130116407A1

  公开（公告）日：2013-05-09

  The invention relates to conjugates of macromolecular carriers and drugs comprising linkers that release the drug or a prodrug through rate-controlled beta-elimination, and methods of making and using the conjugates.

  该发明涉及大分子载体和药物的共轭物，包括通过速率控制的β-消除释放药物或前药的连接剂，以及制备和使用这些共轭物的方法。
• CONTROLLED DRUG RELEASE FROM DENDRIMERS
  申请人：Ashley Gary

  公开号：US20130123461A1

  公开（公告）日：2013-05-16

  The invention relates to compositions that comprise dendrimers useful in medical and veterinary applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the dendrimer through a linkage that releases the drug or a prodrug through controlled beta elimination.

  本发明涉及一种包含树状分子的组合物，该组合物在医疗和兽医应用中有用，能够提供药物的控制释放，例如肽，核酸和小分子。药物通过一个连接与树状分子共价耦合，该连接通过控制的β消除释放药物或前药。
• CONTROLLED RELEASE FROM SOLID SUPPORTS
  申请人：Ashley Gary

  公开号：US20130123487A1

  公开（公告）日：2013-05-16

  The invention relates to solid supports useful in medical applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the solid support through a linkage that releases the drug or a prodrug through controlled beta elimination.

  本发明涉及固体支持在医学应用中的使用，提供药物的控制释放，例如肽、核酸和小分子。药物通过一个连接环节共价耦合到固体支持上，通过受控的β消除释放药物或前药。