(S)-4-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-4-benzyloxycarbonylamino-butyric acid benzyl ester | 872984-12-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-4-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-4-benzyloxycarbonylamino-butyric acid benzyl ester
• CAS: 872984-12-8
• 化学式: C₄₀H₅₁N₅O₉
• 分子量: 745.873
• InChiKey: CWAZCWCPHGBYCP-UIJOFPGHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.12
• 重原子数：
  54.0
• 可旋转键数：
  21.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  192.47
• 氢给体数：
  5.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (S)-4-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-4-benzyloxycarbonylamino-butyric acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以0.11 g的产率得到(4S)-4-amino-4-{(1S)-1-[1-benzylcarbamoyl-1-(2-hydroxyethyl)butylcarbamoyl]-3-dimethylamino-3-oxopropylcarbamoyl}butyric acid
  参考文献：
  名称：

  Engineering d-amino acid containing novel protease inhibitors using catalytic site architecture

  摘要：

  The mechanism of proteolysis by serine proteases is a reasonably well-understood process. Typically, a histidine residue acting as a general base deprotonates the catalytic serine residue and the hydrolytic water molecule. We disclose here, the use of an unnatural D-amino acid as a strategic residue in P1 position, designed de novo based on the architecture of the protease catalytic site to impede the catalytic histidine residue at the stage of acyl-enzyme intermediate. Several probe molecules containing D-homoserine or its derivatives at P1 position are evaluated. Compounds 1, 6, and 8-10 produced up to 57% loss of activity against chymotrypsin. More potent and specific inhibitors could be designed with structure optimization as this strategy is completely general and can be used to design inhibitors against any serine or cysteine protease. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.019
• 作为产物：
  描述：

  (4S)-4-((1S)-1-{1-benzylcarbamoyl-1-[2-(tert-butyldiphenylsiloxy)ethyl]butylcarbamoyl}-3-dimethylamino-3-oxopropylcarbamoyl)-4-(benzyloxycarbonylamino)butyric acid benzyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以60%的产率得到(S)-4-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-4-benzyloxycarbonylamino-butyric acid benzyl ester
  参考文献：
  名称：

  Engineering d-amino acid containing novel protease inhibitors using catalytic site architecture

  摘要：

  The mechanism of proteolysis by serine proteases is a reasonably well-understood process. Typically, a histidine residue acting as a general base deprotonates the catalytic serine residue and the hydrolytic water molecule. We disclose here, the use of an unnatural D-amino acid as a strategic residue in P1 position, designed de novo based on the architecture of the protease catalytic site to impede the catalytic histidine residue at the stage of acyl-enzyme intermediate. Several probe molecules containing D-homoserine or its derivatives at P1 position are evaluated. Compounds 1, 6, and 8-10 produced up to 57% loss of activity against chymotrypsin. More potent and specific inhibitors could be designed with structure optimization as this strategy is completely general and can be used to design inhibitors against any serine or cysteine protease. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.019