4-[[5-carbamimidoyl-1-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]benzimidazol-2-yl]methyl-[4-(1-ethanimidoylpiperidin-4-yl)oxyphenyl]carbamoyl]benzoic acid

• 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: 4-[[5-carbamimidoyl-1-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]benzimidazol-2-yl]methyl-[4-(1-ethanimidoylpiperidin-4-yl)oxyphenyl]carbamoyl]benzoic acid
• 化学式: C₄₀H₄₂N₈O₅
• 分子量: 714.824
• InChiKey: IWDLQXKLSKNLEI-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  191
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(4-硝基苯氧基)四氢-1(2H)-吡啶羧酸叔丁酯 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 硫化氢 、 氢气 、 sodium hydride 、 碳酸氢钠 、 sodium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 三乙胺 、 三氟乙酸 、 碘甲烷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 20.0~90.0 ℃ 、303.98 kPa 条件下， 反应 197.08h， 生成 4-[[5-carbamimidoyl-1-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]benzimidazol-2-yl]methyl-[4-(1-ethanimidoylpiperidin-4-yl)oxyphenyl]carbamoyl]benzoic acid
  参考文献：
  名称：

  Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data

  摘要：

  Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use in determining the role of Epi in the central nervous system. Here we demonstrate that a routinely used assay for screening PNMT inhibitors is not appropriate for those inhibitors having K-i values less than 1 muM. A revised assay has been developed that shows some inhibitors bind two orders of magnitude more tightly than previously reported. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.009

文献信息

• Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data
  作者：Qian Wu、Kevin R Criscione、Gary L Grunewald、Michael J McLeish

  DOI：10.1016/j.bmcl.2004.06.009

  日期：2004.8

  Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use in determining the role of Epi in the central nervous system. Here we demonstrate that a routinely used assay for screening PNMT inhibitors is not appropriate for those inhibitors having K-i values less than 1 muM. A revised assay has been developed that shows some inhibitors bind two orders of magnitude more tightly than previously reported. (C) 2004 Elsevier Ltd. All rights reserved.