3,4-dihydro-2-<2-(dimethylamino)ethyl>-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol acetate | 130266-64-7

• 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: 3,4-dihydro-2-<2-(dimethylamino)ethyl>-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol acetate
• 英文别名: 3,4-Dihydro-2-(2-dimethylaminoethyl)-2,5,7,8-tetramethyl-2H-benzopyran-6-yl acetate；6-Acetyloxy-3,4-dihydro-N,N,2,5,7,8-hexamethyl-2H-1-benzopyran-2-ethanamine；[2-[2-(dimethylamino)ethyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate
• CAS: 130266-64-7
• 化学式: C₁₉H₂₉NO₃
• 分子量: 319.444
• InChiKey: DNRCGFUTOSMVEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-2-<2-(dimethylamino)ethyl>-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol acetate 在 盐酸 、 basic resin AG-1-X₂ 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 3,4-dihydro-6-hydroxy-N,N,N,2,5,7,8-heptamethyl-2H-1-benzopyran-2-ethanaminium chloride
  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
• 作为产物：
  描述：

  2-(2-bromoethyl)-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol 在 2,6-二甲基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3,4-dihydro-2-<2-(dimethylamino)ethyl>-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol acetate
  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：Hoechst Marion Roussel, Inc.

  公开号：US05500444A1

  公开（公告）日：1996-03-19

  This invention relates to quaternary ammonium salts of certain 2H-1-benzopyran derivatives, to the intermediates and processes useful for their preparation, to their free-radical scavenger and cellular protective properties and to their end-use application as therapeutic agents.

  这项发明涉及某些2H-1-苯并吡喃衍生物的季铵盐，以及用于它们的制备的中间体和过程，它们的自由基清除剂和细胞保护性能，以及它们作为治疗剂的最终应用。
• Cholesterol-lowering tocopherol analogs
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05135945A1

  公开（公告）日：1992-08-04

  This invention relates to alkylamino alkylene derivatives of certain 2H-1-benzopyrans useful as plasma cholesterol lowering agents and to their end-use application as therapeutic agents.

  这项发明涉及某些2H-1-苯并吡喁酮的烷基氨基烷基衍生物，可用作降低血浆胆固醇的药物，并涉及它们作为治疗剂的最终应用。
• 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：——
• CHOLESTEROL-LOWERING TOCOPHEROL ANALOGS
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0586518B1

  公开（公告）日：1997-03-12