((S)-1-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-3-methyl-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-2,2-dimethyl-propyl)-carbamic acid benzyl ester | 872984-14-0

• 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)-1-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-3-methyl-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-2,2-dimethyl-propyl)-carbamic acid benzyl ester
• CAS: 872984-14-0
• 化学式: C₃₅H₅₁N₅O₇
• 分子量: 653.819
• InChiKey: VNZDODKBOUDWIP-HVNHSRSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.89
• 重原子数：
  47.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  166.17
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ((S)-1-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-3-methyl-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-2,2-dimethyl-propyl)-carbamic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以0.3 g的产率得到(2S)-2-[(2S)-2-amino-3,3-dimethylbutyryl]-N¹-[1-benzylcarbamoyl-1-(2-hydroxyethyl)-3-methylbutyl]-N⁴,N⁴-dimethylsuccinamide
  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：

  [(S)-2-Dimethylcarbamoyl-1-(3-isobutyl-2-oxo-tetrahydro-furan-3-ylcarbamoyl)-ethyl]-carbamic acid benzyl ester 在 palladium on activated charcoal 咪唑 、 lithium hydroxide 、 四丁基氟化铵 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 ((S)-1-{(S)-1-[1-Benzylcarbamoyl-1-(2-hydroxy-ethyl)-3-methyl-butylcarbamoyl]-2-dimethylcarbamoyl-ethylcarbamoyl}-2,2-dimethyl-propyl)-carbamic 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