3-[(S)-2-(2-Chloro-benzyloxycarbonylamino)-3-methyl-butyrylamino]-5-fluoro-4-oxo-pentanoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 3-[(S)-2-(2-Chloro-benzyloxycarbonylamino)-3-methyl-butyrylamino]-5-fluoro-4-oxo-pentanoic acid
• 英文别名: 3-[[(2S)-2-[(2-chlorophenyl)methoxycarbonylamino]-3-methylbutanoyl]amino]-5-fluoro-4-oxopentanoic acid
• 化学式: C₁₈H₂₂ClFN₂O₆
• 分子量: 416.834
• InChiKey: UDJGEZJRKWTPOZ-VYIIXAMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  邻氯苄醇 在 4-二甲氨基吡啶 、 sodium hydroxide 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙醚 为溶剂， 生成 3-[(S)-2-(2-Chloro-benzyloxycarbonylamino)-3-methyl-butyrylamino]-5-fluoro-4-oxo-pentanoic acid
  参考文献：
  名称：

  Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: SAR of the N-protecting group

  摘要：

  This article describes the synthesis and biological evaluation of a group of N-protected Val-Asp-fmk as caspase inhibitors. The protecting group was found to contribute to caspase-3 inhibiting activity, and compounds with a large group such as Cbz are more active than compounds with a small group such as Ac. Compounds with more hydrophobic protecting groups were found to be more active in cell apoptosis protection assays, probably due to increased cell permeability. MX1122,2,4-di-Cl-Cbz-Val-Aspfmk, is identified as a potent broad-spectrum caspase inhibitor and is selective for caspases versus other proteases, with good activity in the cell apoptosis protection assays as well as good efficacy in the mouse liver apoptosis model. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.027

文献信息

• Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: SAR of the N-protecting group
  作者：Sui Xiong Cai、Lufeng Guan、Shaojuan Jia、Yan Wang、Wu Yang、Ben Tseng、John Drewe

  DOI：10.1016/j.bmcl.2004.08.027

  日期：2004.11

  This article describes the synthesis and biological evaluation of a group of N-protected Val-Asp-fmk as caspase inhibitors. The protecting group was found to contribute to caspase-3 inhibiting activity, and compounds with a large group such as Cbz are more active than compounds with a small group such as Ac. Compounds with more hydrophobic protecting groups were found to be more active in cell apoptosis protection assays, probably due to increased cell permeability. MX1122,2,4-di-Cl-Cbz-Val-Aspfmk, is identified as a potent broad-spectrum caspase inhibitor and is selective for caspases versus other proteases, with good activity in the cell apoptosis protection assays as well as good efficacy in the mouse liver apoptosis model. (C) 2004 Elsevier Ltd. All rights reserved.