5,7-dimethoxy-4'-(3-aminobut-1-yl)flavone | 1407626-61-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 5,7-dimethoxy-4'-(3-aminobut-1-yl)flavone
• 英文别名: 2-[4-(4-Aminobutyl)phenyl]-5,7-dimethoxychromen-4-one；2-[4-(4-aminobutyl)phenyl]-5,7-dimethoxychromen-4-one
• CAS: 1407626-61-2
• 化学式: C₂₁H₂₃NO₄
• 分子量: 353.418
• InChiKey: RAFRUADJHVMXOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,7-dimethoxy-4'-(3-aminobut-1-yl)flavone 在 三溴化硼 、 正丁胺 作用下， 以 二氯甲烷 、 氯仿 、 甲醇 为溶剂， 反应 24.0h， 以31%的产率得到5,7-dihydroxy-4'-(3-aminobut-1-yl)flavone
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Inhibitors of Pyruvate Phosphate Dikinase

  摘要：

  Pyruvate phosphate dikinase (PPDK) catalyzes the phosphorylation reaction of pyruvate that forms phosphoenolpyruvate (PEP) via two partial reactions: PPDK + ATP + P-i -> PPDK-P + AMP + PPi and PPDK-P + pyruvate(i) -> PEP + PPDK. Based on its role in the metabolism of microbial human pathogens, PPDK is a potential drug target. A screen of substances that bind to the PPDK ATP-grasp domain active site revealed that flavone analogues are potent inhibitors of the Clostridium symbiosum PPDK. In silico modeling studies suggested that placement of a 3-6 carbon-tethered ammonium substituent at the 3'- or 4'-positions of 5,7-dihydroxyflavones would result in favorable electrostatic interactions with the PPDK Mg-ATP binding site. As a result, polymethylene-tethered amine derivatives of 5,7-dihydroxyflavones were prepared. Steady-state kinetic analysis of these substances demonstrates that the 4'-aminohexyl-5,7-dyhydroxyflavone 10 is a potent competitive PPDK inhibitor (K-i = 1.6 +/- 0.1 mu M). Single turnover experiments were conducted using 4'-aminopropyl-5,7-dihydroxyflavone 7 to show that this flavone specifically targets the ATP binding site and inhibits catalysis of only the PPDK + ATP + P-i -> PPDK-P + AMP PP, partial reaction. Finally, the 4'-aminopbutyl-5,7-dihydroxyflavone 8 displays selectivity for inhibition of PPDK versus other enzymes that utilize ATP and NAD.

  DOI：

  10.1021/jo3018473
• 作为产物：
  描述：

  2-羟基-4,6-二甲氧基苯乙酮 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 一水合肼 、 三乙胺 、 三对苯甲基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 5,7-dimethoxy-4'-(3-aminobut-1-yl)flavone
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Inhibitors of Pyruvate Phosphate Dikinase

  摘要：

  Pyruvate phosphate dikinase (PPDK) catalyzes the phosphorylation reaction of pyruvate that forms phosphoenolpyruvate (PEP) via two partial reactions: PPDK + ATP + P-i -> PPDK-P + AMP + PPi and PPDK-P + pyruvate(i) -> PEP + PPDK. Based on its role in the metabolism of microbial human pathogens, PPDK is a potential drug target. A screen of substances that bind to the PPDK ATP-grasp domain active site revealed that flavone analogues are potent inhibitors of the Clostridium symbiosum PPDK. In silico modeling studies suggested that placement of a 3-6 carbon-tethered ammonium substituent at the 3'- or 4'-positions of 5,7-dihydroxyflavones would result in favorable electrostatic interactions with the PPDK Mg-ATP binding site. As a result, polymethylene-tethered amine derivatives of 5,7-dihydroxyflavones were prepared. Steady-state kinetic analysis of these substances demonstrates that the 4'-aminohexyl-5,7-dyhydroxyflavone 10 is a potent competitive PPDK inhibitor (K-i = 1.6 +/- 0.1 mu M). Single turnover experiments were conducted using 4'-aminopropyl-5,7-dihydroxyflavone 7 to show that this flavone specifically targets the ATP binding site and inhibits catalysis of only the PPDK + ATP + P-i -> PPDK-P + AMP PP, partial reaction. Finally, the 4'-aminopbutyl-5,7-dihydroxyflavone 8 displays selectivity for inhibition of PPDK versus other enzymes that utilize ATP and NAD.

  DOI：

  10.1021/jo3018473

文献信息

• Design, Synthesis, and Evaluation of Inhibitors of Pyruvate Phosphate Dikinase
  作者：Chun Wu、Debra Dunaway-Mariano、Patrick S. Mariano

  DOI：10.1021/jo3018473

  日期：2013.3.1

  Pyruvate phosphate dikinase (PPDK) catalyzes the phosphorylation reaction of pyruvate that forms phosphoenolpyruvate (PEP) via two partial reactions: PPDK + ATP + P-i -> PPDK-P + AMP + PPi and PPDK-P + pyruvate(i) -> PEP + PPDK. Based on its role in the metabolism of microbial human pathogens, PPDK is a potential drug target. A screen of substances that bind to the PPDK ATP-grasp domain active site revealed that flavone analogues are potent inhibitors of the Clostridium symbiosum PPDK. In silico modeling studies suggested that placement of a 3-6 carbon-tethered ammonium substituent at the 3'- or 4'-positions of 5,7-dihydroxyflavones would result in favorable electrostatic interactions with the PPDK Mg-ATP binding site. As a result, polymethylene-tethered amine derivatives of 5,7-dihydroxyflavones were prepared. Steady-state kinetic analysis of these substances demonstrates that the 4'-aminohexyl-5,7-dyhydroxyflavone 10 is a potent competitive PPDK inhibitor (K-i = 1.6 +/- 0.1 mu M). Single turnover experiments were conducted using 4'-aminopropyl-5,7-dihydroxyflavone 7 to show that this flavone specifically targets the ATP binding site and inhibits catalysis of only the PPDK + ATP + P-i -> PPDK-P + AMP PP, partial reaction. Finally, the 4'-aminopbutyl-5,7-dihydroxyflavone 8 displays selectivity for inhibition of PPDK versus other enzymes that utilize ATP and NAD.