2-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl-N,N,N-trimethylammonium bromide | 130518-36-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl-N,N,N-trimethylammonium bromide
• 英文别名: 3,4-dihydro-6-hydroxy-N,N,N,2,5,7,8-heptamethyl-2H-1-benzopyran-2-ethanaminium bromide；2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2 H-1-benzopyran-2-yl)ethyl-N,N,N-trimethylammonium bromide；2-(6-Hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)ethyl-trimethylazanium;bromide
• CAS: 130518-36-4
• 化学式: Br*C₁₈H₃₀NO₂
• 分子量: 372.346
• InChiKey: RNKIPVYVFKGZEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-ethanol 在 溴 、 三苯基膦 作用下， 以 二氯甲烷 、 丁酮 为溶剂， 反应 65.0h， 生成 2-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl-N,N,N-trimethylammonium bromide
  参考文献：
  名称：

  A cardioselective, hydrophilic N,N,N-trimethylethanaminium .alpha.-tocopherol analog that reduces myocardial infarct size

  摘要：

  The alpha-tocopherol analogue 3,4-dihydro-6-hydroxy-N,N,N,2,5,7,8-heptamethyl-2H-1-benzopyran-2-ethanaminium 4-methylbenzenesulfonate (1a, MDL 73404) and its O-acetate 1b (MDL 74270) were synthesized. Compound 1a was found to be hydrophilic (log P = -0.60) and to prevent lipid autoxidation in rat brain homogenate with an IC50 of 1.7 +/- 0.9-mu-M. Tissue distribution studies with [C-14]-1b in rats (1 mg/kg iv) showed that radioactivity accumulates in the heart (ratio 20:1 vs blood after 1 h). Infusion of 1 mg/kg per h of 1b bromide reduced infarct size by 54% in rats subjected to coronary artery occlusion for 60 min followed by reperfusion for 30 min, compared to saline-infused controls. By comparison, the tertiary amine analogue 5 was found not to accumulate in heart tissue, to be an equally effective free-radical scavenger in vitro, but to require a higher dose to reduce infarct size in rats. This shows that the cardioselectivity of compound 1 contributes to its potency in salvaging myocardial tissue in rats after ischemia and reperfusion.

  DOI：

  10.1021/jm00105a040

文献信息

• Cardioprotective tocopherol analogs
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0369874B1

  公开（公告）日：1995-02-22
• GRISAR, J. MARTIN;PETTY, MARGARET A.;BOLKENIUS, FRANK N.;DOW, JAMES;WAGNE+, J. MED. CHEM., 34,(1991) N, C. 257-260
  作者：GRISAR, J. MARTIN、PETTY, MARGARET A.、BOLKENIUS, FRANK N.、DOW, JAMES、WAGNE+

  DOI：——

  日期：——
• GRISAR, J. MARTIN;PETTY, MARGARET;BOLKENIUS, FRANK
  作者：GRISAR, J. MARTIN、PETTY, MARGARET、BOLKENIUS, FRANK

  DOI：——

  日期：——
• US5500444A
  申请人：——

  公开号：US5500444A

  公开（公告）日：1996-03-19
• A cardioselective, hydrophilic N,N,N-trimethylethanaminium .alpha.-tocopherol analog that reduces myocardial infarct size
  作者：J. Martin Grisar、Margaret A. Petty、Frank N. Bolkenius、James Dow、Joseph Wagner、Eugene R. Wagner、Klaus D. Haegele、Wybren De Jong

  DOI：10.1021/jm00105a040

  日期：1991.1

  The alpha-tocopherol analogue 3,4-dihydro-6-hydroxy-N,N,N,2,5,7,8-heptamethyl-2H-1-benzopyran-2-ethanaminium 4-methylbenzenesulfonate (1a, MDL 73404) and its O-acetate 1b (MDL 74270) were synthesized. Compound 1a was found to be hydrophilic (log P = -0.60) and to prevent lipid autoxidation in rat brain homogenate with an IC50 of 1.7 +/- 0.9-mu-M. Tissue distribution studies with [C-14]-1b in rats (1 mg/kg iv) showed that radioactivity accumulates in the heart (ratio 20:1 vs blood after 1 h). Infusion of 1 mg/kg per h of 1b bromide reduced infarct size by 54% in rats subjected to coronary artery occlusion for 60 min followed by reperfusion for 30 min, compared to saline-infused controls. By comparison, the tertiary amine analogue 5 was found not to accumulate in heart tissue, to be an equally effective free-radical scavenger in vitro, but to require a higher dose to reduce infarct size in rats. This shows that the cardioselectivity of compound 1 contributes to its potency in salvaging myocardial tissue in rats after ischemia and reperfusion.