O-[6-azidohexyl]-N-[4’-(diethylcarbamoyl)phenyl]carbamate | 1492926-61-0

• 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: O-[6-azidohexyl]-N-[4’-(diethylcarbamoyl)phenyl]carbamate
• CAS: 1492926-61-0
• 化学式: C₁₈H₂₇N₅O₃
• 分子量: 361.444
• InChiKey: CPBPIYQSCTTYDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.59
• 重原子数：
  26.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  107.4
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  O-[6-azidohexyl]-N-[4’-(diethylcarbamoyl)phenyl]carbamate 在 吡啶 、 三甲基氯硅烷 、 potassium tert-butylate 、 溶剂黄146 、 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 27.25h， 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：

  6-叠氮基-1-己醇 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.67h， 生成 O-[6-azidohexyl]-N-[4’-(diethylcarbamoyl)phenyl]carbamate
  参考文献：
  名称：

  β-Eliminative Releasable Linkers Adapted for Bioconjugation of Macromolecules to Phenols

  摘要：

  We recently reported a chemical approach for half-life extension that utilizes sets of releasable linkers to attach drugs to macromolecules via a cleavable carbamate group (Santi et al., Proc. Nat. Acad. Sci. U.S.A. 2012, 109, 6211-6216). The linkers undergo a beta-elimination cleavage to release the free, native amine-containing drug. A limitation of the technology is the requirement for an amino group on the drug in order to form the carbamate bond, since most small molecules do not have an amine functional group. Here, we describe an approach to adapt these same beta-elimination carbamate linkers so they can be used to connect other acidic heteroatoms, in particular, phenolic hydroxyl groups. The approach utilizes a methylene adaptor to connect the drug to the carbamate nitrogen, and an electron-withdrawing group attached to carbamate nitrogen to stabilize the system against a pH-independent spontaneous cleavage. Carbamate cleavage is driven by beta-elimination to give a carboxylated aryl amino Mannich base which rapidly collapses to give the free drug, an aryl amine, and formaldehyde.

  DOI：

  10.1021/bc4002882