O-[1-(phenylsulfonyl)-7-azido-2-heptyl]-N-[4-(morpholinosulfonyl)phenyl]carbamate | 1346434-60-3

• 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-[1-(phenylsulfonyl)-7-azido-2-heptyl]-N-[4-(morpholinosulfonyl)phenyl]carbamate
• 英文别名: [7-azido-1-(benzenesulfonyl)heptan-2-yl] N-(4-morpholin-4-ylsulfonylphenyl)carbamate
• CAS: 1346434-60-3
• 化学式: C₂₄H₃₁N₅O₇S₂
• 分子量: 565.671
• InChiKey: SIMUAPYMHSVCSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  150
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 O-[1-(phenylsulfonyl)-7-azido-2-heptyl]-N-[4-(morpholinosulfonyl)phenyl]carbamate 在 三甲基氯硅烷 作用下， 以 四氢呋喃 为溶剂， 反应 41.0h， 生成
  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
• 作为产物：
  描述：

  1-(phenylsulfonyl)-7-azido-2-heptanol 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.67h， 生成 O-[1-(phenylsulfonyl)-7-azido-2-heptyl]-N-[4-(morpholinosulfonyl)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

文献信息

• [EN] SULFONE LINKERS<br/>[FR] COUPLEURS AU SULFONE
  申请人：PROLYNX LLC

  公开号：WO2013036857A1

  公开（公告）日：2013-03-14

  Sulfone linkers which couple drugs to carriers of various types are described. These linkers permit the release of the drug over time in a controlled manner. The release occurs through beta-elimination, and does not require enzymatic cleavage. Products of the linkers with both drugs and macromolecules and methods of using them are described as well.

  研究描述了将药物与各种载体耦合的砜键连接剂。这些连接剂允许药物以受控方式随时间释放。释放是通过β-消除而发生的，并不需要酶解。还描述了连接剂与药物和大分子的产物以及它们的使用方法。
• HYDROGELS WITH BIODEGRADABLE CROSSLINKING
  申请人：ProLynx LLC

  公开号：US20170312368A1

  公开（公告）日：2017-11-02

  Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals.

  描述了在适当的pH和温度条件下，由于交联化合物通过消除反应而降解的水凝胶。这些水凝胶可以用于输送各种药剂，如药物。
• 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。
• Hydrogels with biodegradable crosslinking
  申请人：ProLynx LLC

  公开号：US10398779B2

  公开（公告）日：2019-09-03

  Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals.

  本文介绍了在适当的 pH 值和温度条件下，交联化合物通过消除反应裂解而降解的水凝胶。这种水凝胶可用于输送各种药剂，如药物。
• CONTROLLED RELEASE OF ACTIVE COMPOUNDS FROM MACROMOLECULAR CONJUGATES
  申请人：Prolynx LLC

  公开号：EP2566335B1

  公开（公告）日：2016-06-29