N-(3,4-Dihydroxyphenyl)-succinamid-saeure | 71573-13-2

• 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: N-(3,4-Dihydroxyphenyl)-succinamid-saeure
• 英文别名: 4-(3',4'-hydroxy-phenylamino)-4-oxo-butanoic acid；4-(3,4-Dihydroxyanilino)-4-oxobutanoic acid；4-(3,4-dihydroxyanilino)-4-oxobutanoic acid
• CAS: 71573-13-2
• 化学式: C₁₀H₁₁NO₅
• 分子量: 225.201
• InChiKey: GRBWXJFBMIFOOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-羟基-苯基氨基)-4-氧代-丁酸 、 N-(3,4-Dihydroxyphenyl)-succinamid-saeure 、 N,O-双(三甲基硅烷基)三氟乙酰胺 以 乙酸乙酯 为溶剂， 反应 1.0h， 生成 、
  参考文献：
  名称：

  Homology modeling and molecular dynamics of CYP1A1 and CYP2B1 to explore the metabolism of aryl derivatives by docking and experimental assays

  摘要：

  Since many drugs are metabolized by cytochrome P450 (CYP450), biotransformation studies using these enzymes are valuable in drug development. In this work, the biotransformation by CYP1A1 and CYP2B1 of two acetylcholinesterase (AChE) inhibitors, 4-(4'-hydroxy-phenylamino)-4-oxo propanoic acid (A) and 1H-pyrrolidine-1-(4'-hydroxy-phenyl)-2,5-dione (B), was investigated through docking and molecular dynamics (MD) simulations and by experimental methods using rat liver microsomes pretreated with beta-naphthoflavone and phenobarbital (CYP1A1 and CYP2B1 inducers, respectively). The target proteins were initially built by homology modeling, and the resulting three-dimensional structures were refined by MD to obtain fifteen snapshots of each P450 isoform. These snapshots were used to dock compounds A and B as well as the reference compound acetaminophen (APAP). We confirmed that APAP produces a toxic intermediate (N-acetyl-p-benzoquinone imine) upon interaction of its amide group with the heme iron of CYP1A1. However, neither A nor B presented this kind of interaction within any snapshot with CYP1A1. On the other hand, when APAP, A and B were docked on CYP2B1, their hydroxyl group was located near the heme iron on the snapshot at 3.5 ns. Furthermore, B maintained the same position on all snapshots of this isoform. Therefore, theoretical results suggests that A and B do not generate toxic metabolites. These data were supported by HPLC analysis showing only one metabolite from A and B, which was identified by GC-MS as the hydroxylated product. Altogether, our results suggest that neither test compound is toxic. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.055

文献信息

• Homology modeling and molecular dynamics of CYP1A1 and CYP2B1 to explore the metabolism of aryl derivatives by docking and experimental assays
  作者：Martha C. Rosales-Hernández、Jessica E. Mendieta-Wejebe、José G. Trujillo-Ferrara、José Correa-Basurto

  DOI：10.1016/j.ejmech.2010.07.055

  日期：2010.11

  Since many drugs are metabolized by cytochrome P450 (CYP450), biotransformation studies using these enzymes are valuable in drug development. In this work, the biotransformation by CYP1A1 and CYP2B1 of two acetylcholinesterase (AChE) inhibitors, 4-(4'-hydroxy-phenylamino)-4-oxo propanoic acid (A) and 1H-pyrrolidine-1-(4'-hydroxy-phenyl)-2,5-dione (B), was investigated through docking and molecular dynamics (MD) simulations and by experimental methods using rat liver microsomes pretreated with beta-naphthoflavone and phenobarbital (CYP1A1 and CYP2B1 inducers, respectively). The target proteins were initially built by homology modeling, and the resulting three-dimensional structures were refined by MD to obtain fifteen snapshots of each P450 isoform. These snapshots were used to dock compounds A and B as well as the reference compound acetaminophen (APAP). We confirmed that APAP produces a toxic intermediate (N-acetyl-p-benzoquinone imine) upon interaction of its amide group with the heme iron of CYP1A1. However, neither A nor B presented this kind of interaction within any snapshot with CYP1A1. On the other hand, when APAP, A and B were docked on CYP2B1, their hydroxyl group was located near the heme iron on the snapshot at 3.5 ns. Furthermore, B maintained the same position on all snapshots of this isoform. Therefore, theoretical results suggests that A and B do not generate toxic metabolites. These data were supported by HPLC analysis showing only one metabolite from A and B, which was identified by GC-MS as the hydroxylated product. Altogether, our results suggest that neither test compound is toxic. (C) 2010 Elsevier Masson SAS. All rights reserved.