H2N-Asp(O-tBu)-CH2-(1-phenyl-3-(trifluoromethyl)pyrazol-5-yloxy)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: H2N-Asp(O-tBu)-CH2-(1-phenyl-3-(trifluoromethyl)pyrazol-5-yloxy)
• 英文别名: tert-butyl (3S)-3-amino-4-oxo-5-[2-phenyl-5-(trifluoromethyl)pyrazol-3-yl]oxypentanoate
• 化学式: C₁₉H₂₂F₃N₃O₄
• 分子量: 413.397
• InChiKey: NDEXAKFFBMKRNV-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  96.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  H2N-Asp(O-tBu)-CH2-(1-phenyl-3-(trifluoromethyl)pyrazol-5-yloxy) 、 (S)-3-甲基-2-(苯基氨基甲酰基)丁酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 (S)-3-((S)-3-Methyl-2-phenylcarbamoyloxy-butyrylamino)-4-oxo-5-(2-phenyl-5-trifluoromethyl-2H-pyrazol-3-yloxy)-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: peptidomimetic replacement of the P2 α-amino acid by a α-hydroxy acid

  摘要：

  As a continuation of our SAR studies of dipeptidyl aspartyl-fmk as caspase inhibitors, we explored the replacement of the P-2 alpha-amino acid by a peptidomimetic alpha-hydroxy acid. These alpha-carbamoyl-alkylcarbonyl-aspartyl fluoromethylketones were found to be potent caspase inhibitors, and the SAR of these compounds is similar to the corresponding dipeptidyl aspartyl-fmk. MX1153, (S)-3-methyl-2-(phenylcarbamoyl)butanoyl-Asp-fmk, is identified as a potent broad-spectrum caspase inhibitor, and is selective for caspases versus other proteases. MX1153 also has good activity in the cell apoptosis protection assays and is active in the mouse liver apoptosis model. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.007

文献信息

• Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: peptidomimetic replacement of the P2 α-amino acid by a α-hydroxy acid
  作者：Yan Wang、Lufeng Guan、Shaojuan Jia、Ben Tseng、John Drewe、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2005.01.007

  日期：2005.3

  As a continuation of our SAR studies of dipeptidyl aspartyl-fmk as caspase inhibitors, we explored the replacement of the P-2 alpha-amino acid by a peptidomimetic alpha-hydroxy acid. These alpha-carbamoyl-alkylcarbonyl-aspartyl fluoromethylketones were found to be potent caspase inhibitors, and the SAR of these compounds is similar to the corresponding dipeptidyl aspartyl-fmk. MX1153, (S)-3-methyl-2-(phenylcarbamoyl)butanoyl-Asp-fmk, is identified as a potent broad-spectrum caspase inhibitor, and is selective for caspases versus other proteases. MX1153 also has good activity in the cell apoptosis protection assays and is active in the mouse liver apoptosis model. (c) 2005 Elsevier Ltd. All rights reserved.