tert-butyl (S)-3-((2S,3S)-2-(((benzyloxy)carbonyl)amino)-3-methylpentanamido)-4-oxobutanoate | 1246261-49-3

• 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: tert-butyl (S)-3-((2S,3S)-2-(((benzyloxy)carbonyl)amino)-3-methylpentanamido)-4-oxobutanoate
• CAS: 1246261-49-3
• 化学式: C₂₂H₃₂N₂O₆
• 分子量: 420.506
• InChiKey: RHAFPNQDUADQFY-IEZWGBDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.74
• 重原子数：
  30.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  110.8
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  二乙基(甲基磺酰基)膦 、 tert-butyl (S)-3-((2S,3S)-2-(((benzyloxy)carbonyl)amino)-3-methylpentanamido)-4-oxobutanoate 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 2.0h， 以47%的产率得到tert-butyl (S)-3-((2S,3S)-2-(((benzyloxy)carbonyl)amino)-3-methylpentanamido)-5-(methylsulfonyl)pent-4-enoate
  参考文献：
  名称：

  Synthesis and evaluation of vinyl sulfones as caspase-3 inhibitors. A structure–activity study

  摘要：

  The first structure activity relationship study of vinyl sulfones as caspase-3 inhibitors is reported. A series of 12 vinyl sulfones was synthesized and evaluated for two downstream caspases (caspases-3 and -7). Dipeptidyl derivatives were significantly superior to their counterparts containing only Asp at P(1), as caspase-3 inhibitors. Fmoc-Val-Asp-trans-CH=CH-SO(2)Me was the most potent inhibitor of caspase-3 in the series, with a IC(50) of 29 mu M and a second-order rate constant of inactivation, k(inact)/(K)i, of 1.5 M(-1) s(-1) Computational studies suggest that the second amino acid occupies position S(3) of the enzyme. In addition, Fmoc-Val-Asp-trans-CH=CH-SO(2)Ph was inactive for caspase-7 for the tested concentrations. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.039