(R,E)-3-((3,7-dimethylocta-2,6-dien-1-yl)thio)-2-(2-phenoxybenzamido)propanoic acid | 1354017-61-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R,E)-3-((3,7-dimethylocta-2,6-dien-1-yl)thio)-2-(2-phenoxybenzamido)propanoic acid
• 英文别名: (2R)-3-[(2E)-3,7-dimethylocta-2,6-dienyl]sulfanyl-2-[(2-phenoxybenzoyl)amino]propanoic acid
• CAS: 1354017-61-0
• 化学式: C₂₆H₃₁NO₄S
• 分子量: 453.602
• InChiKey: OEYNXNQXSVCGFH-UEAVEIDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  Cys(Ger)-OMe 在 甲醇 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (R,E)-3-((3,7-dimethylocta-2,6-dien-1-yl)thio)-2-(2-phenoxybenzamido)propanoic acid
  参考文献：
  名称：

  Amide-modified prenylcysteine based Icmt inhibitors: Structure–activity relationships, kinetic analysis and cellular characterization

  摘要：

  Human protein isoprenylcysteine carboxyl methyltransferase (hIcmt) is the enzyme responsible for the alpha-carboxyl methylation of the C-terminal isoprenylated cysteine of CaaX proteins, including Ras proteins. This specific posttranslational methylation event has been shown to be important for cellular transformation by oncogenic Ras isoforms. This finding led to interest in hIcmt inhibitors as potential anti-cancer agents. Previous analog studies based on N-acetyl-S-farnesylcysteine identified two prenylcysteine-based low micromolar inhibitors (1a and 1b) of hIcmt, each bearing a phenoxyphenyl amide modification. In this study, a focused library of analogs of 1a and 1b was synthesized and screened versus hIcmt, delineating structural features important for inhibition. Kinetic characterization of the most potent analogs 1a and 1b established that both inhibitors exhibited mixed-mode inhibition and that the competitive component predominated. Using the Cheng-Prusoff method, the K-i values were determined from the IC50 values. Analog 1a has a K-IC of 1.4 +/- 0.2 mu M and a K-IU of 4.8 +/- 0.5 mu M while 1b has a K-IC of 0.5 +/- 0.07 mu M and a K-IU of 1.9 +/- 0.2 mu M. Cellular evaluation of 1b revealed that it alters the subcellular localization of GFP-KRas, and also inhibits both Ras activation and Erk phosphorylation in Jurkat cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.087