{2-[benzenesulfonyl(benzyl)amino]ethyl}{3-[benzenesulfonyl(benzyl)amino]propyl}carbamic acid tert-butyl ester | 1076203-07-0

• 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: {2-[benzenesulfonyl(benzyl)amino]ethyl}{3-[benzenesulfonyl(benzyl)amino]propyl}carbamic acid tert-butyl ester
• CAS: 1076203-07-0
• 化学式: C₃₆H₄₃N₃O₆S₂
• 分子量: 677.886
• InChiKey: JJKPKFZZCKWKJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  47.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  104.3
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  {2-[benzenesulfonyl(benzyl)amino]ethyl}{3-[benzenesulfonyl(benzyl)amino]propyl}carbamic acid tert-butyl ester 在 盐酸 作用下， 以 乙醚 为溶剂， 以86%的产率得到{2-[(phenylsulfonyl)(benzyl)amino]ethyl}{3-[(phenylsulfonyl)(benzyl)amino]propyl}amine hydrochloride
  参考文献：
  名称：

  Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors

  摘要：

  Due to the important role that aspartic proteases play in many patho-physiological processes, they have intensively been targeted by modern drug development. However, up to now, only for two family members, renin and HIV protease, approved drugs are available. Inhibitor development, mostly guided by mimicking the natural peptide substrates, resulted in very potent inhibitors for several targets, but the pharmacokinetic properties of these compounds were often not optimal. Herein we report a novel approach for lead structure discovery of non-peptidic aspartic protease inhibitors using easily accessible achiral linear oligoamines as starting point. An initial library comprising 11 inhibitors was developed and screened against six selected aspartic proteases. Several hits could be identified, among them selective as well as rather promiscuous inhibitors. The design concept was confirmed by determination of the crystal structure of two derivatives in complex with the HIV-1 protease, and represents a promising basis for the further inhibitor development. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.012
• 作为产物：
  描述：

  [2-(benzenesulfonylamino)ethyl][3-(benzenesulfonylamino)propyl]carbamic acid tert-butyl ester 、 溴甲苯 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以66%的产率得到{2-[benzenesulfonyl(benzyl)amino]ethyl}{3-[benzenesulfonyl(benzyl)amino]propyl}carbamic acid tert-butyl ester
  参考文献：
  名称：

  Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors

  摘要：

  Due to the important role that aspartic proteases play in many patho-physiological processes, they have intensively been targeted by modern drug development. However, up to now, only for two family members, renin and HIV protease, approved drugs are available. Inhibitor development, mostly guided by mimicking the natural peptide substrates, resulted in very potent inhibitors for several targets, but the pharmacokinetic properties of these compounds were often not optimal. Herein we report a novel approach for lead structure discovery of non-peptidic aspartic protease inhibitors using easily accessible achiral linear oligoamines as starting point. An initial library comprising 11 inhibitors was developed and screened against six selected aspartic proteases. Several hits could be identified, among them selective as well as rather promiscuous inhibitors. The design concept was confirmed by determination of the crystal structure of two derivatives in complex with the HIV-1 protease, and represents a promising basis for the further inhibitor development. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.012