3,4-dihydro-2-<2-(dimethylamino)ethyl>-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol | 130573-34-1

• 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
• 英文别名: 3,4-dihydro-2-(2-dimethylaminoethyl)-2,5,7,8-tetra-methyl-2H-1-benzopyran-6-ol；3,4-dihydro-2-(2-dimethylaminoethyl)-2,5,7,8-tetramehtyl-2H-1-benzopyran-6-ol；2-[2-(Dimethylamino)ethyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-ol
• CAS: 130573-34-1
• 化学式: C₁₇H₂₇NO₂
• 分子量: 277.407
• InChiKey: DYNIOWJSSKCSFL-UHFFFAOYSA-N

物化性质

• 沸点：
  398.2±42.0 °C(Predicted)
• 密度：
  1.024±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

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 以 乙腈 为溶剂， 反应 1.5h， 生成 (2S)-(-)-3,4-dihydro-6-hydroxy-N,N,N,-2,5,7,8-heptamethyl-2H-1-benzopyran-2-ethanaminium 4-methylbenzenesulfonate
  参考文献：
  名称：

  Cardioselective Ammonium, Phosphonium, and Sulfonium Analogs of .alpha.-Tocopherol and Ascorbic Acid That Inhibit in Vitro and ex Vivo Lipid Peroxidation and Scavenge Superoxide Radicals

  摘要：

  Analogues of alpha-tocopherol and ascorbic acid with permanently cationic substituents, i.e., phosphonium (8, 9), sulfonium (11), acylhydrazinium (13, 14), and ammonium (1, 16, 21), were synthesized, and the 2R and 2S enantiomers of the alpha-tocopherol analogues 1, 8, 11, and 13 were separated. The compounds were found to scavenge lipoperoxyl and superoxide radicals in vitro and accumulate in heart tissue (cardioselectivity) as demonstrated by measurement of ex vivo inhibition of lipid peroxidation in mouse heart homogenates and confirmed by HPLC determination of drug concentrations for 1 and 11. The 2R and 2S enantiomers of 1 inhibited ex vivo lipid peroxidation to an equal extent. Thus the in vivo uptake into myocytes (cardioselectivity) is independent of the geometry at the chiral center and common to permanently cationic compounds.

  DOI：

  10.1021/jm00015a010
• 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3,4-dihydro-2-<2-(dimethylamino)ethyl>-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol
  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

• 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：——
• CHOLESTEROL-LOWERING TOCOPHEROL ANALOGS
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0586518B1

  公开（公告）日：1997-03-12
• US5135945A
  申请人：——

  公开号：US5135945A

  公开（公告）日：1992-08-04
• US5500444A
  申请人：——

  公开号：US5500444A

  公开（公告）日：1996-03-19
• [EN] CHOLESTEROL-LOWERING TOCOPHEROL ANALOGS
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：WO1992021336A1

  公开（公告）日：1992-12-10

  (EN) This invention relates to alkylamino alkylene derivatives of certain 2$i(H)-1-benzopyrans useful as plasma cholesterol lowering agents and to their end-use application as therapeutic agents.(FR) Cette invention concerne des alkylamino alkylènes derivés de certains 2$i(H)-1-benzopyrannes utiles en tant qu'agents abaissant le taux de cholestérol dans le plasma et leur utilisation finale en tant qu'agents thérapeutiques.