(3R)-3-[(2S)-2-hydroxy-2-(4-methylphenyl)ethyl]-2-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octane-1-carbonyl]-2,3-dihydroisoindol-1-one | 1338225-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (3R)-3-[(2S)-2-hydroxy-2-(4-methylphenyl)ethyl]-2-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octane-1-carbonyl]-2,3-dihydroisoindol-1-one
• CAS: 1338225-74-3
• 化学式: C₂₈H₃₁NO₅
• 分子量: 461.558
• InChiKey: UYAAZSQVRDMHPI-HDYVOGQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.51
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  83.91
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (3R)-3-[(2S)-2-hydroxy-2-(4-methylphenyl)ethyl]-2-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octane-1-carbonyl]-2,3-dihydroisoindol-1-one 在 盐酸 、 锂硼氢 、 dimethyl sulfide borane 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 水 为溶剂， 反应 18.5h， 生成 (1S)-2-[(1R)-2-methyl-2,3-dihydro-1H-isoindol-1-yl]-1-(4-methylphenyl)ethanol hydrochloride
  参考文献：
  名称：

  Synthesis of a series of γ-amino alcohols comprising an N-methyl isoindoline moiety and their evaluation as NMDA receptor antagonists

  摘要：

  We report a series of new stereoisomeric gamma-amino alcohols comprising an N-methyl isoindoline moiety as ligands for the ifenprodil binding site of the NMDA receptor. Among the four series of stereoisomers, 8a-c, 9a-c, 10a-c, and 11a-c, synthesised, the highest potencies and NMDA-NR2B subtype selectivity was found for the methyl derivative 11a and the chloro derivative 11c, both possessing the [1S,1'S] configuration. However, additional moderate potency of 11a and 11c at the hERG channel with values of 2.6 +/- 2.4% and 1.6 +/- 2.0%, respectively, rendered them unsuitable for medical use. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.119
• 作为产物：
  描述：

  (3R)-3-[2-(4-methylphenyl)-2-oxoethyl]-2-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octane-1-carbonyl]-2,3-dihydroisoindol-1-one 在 Li[Al(tBuO)3H] 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以89%的产率得到(3R)-3-[(2S)-2-hydroxy-2-(4-methylphenyl)ethyl]-2-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octane-1-carbonyl]-2,3-dihydroisoindol-1-one
  参考文献：
  名称：

  Synthesis of a series of γ-amino alcohols comprising an N-methyl isoindoline moiety and their evaluation as NMDA receptor antagonists

  摘要：

  We report a series of new stereoisomeric gamma-amino alcohols comprising an N-methyl isoindoline moiety as ligands for the ifenprodil binding site of the NMDA receptor. Among the four series of stereoisomers, 8a-c, 9a-c, 10a-c, and 11a-c, synthesised, the highest potencies and NMDA-NR2B subtype selectivity was found for the methyl derivative 11a and the chloro derivative 11c, both possessing the [1S,1'S] configuration. However, additional moderate potency of 11a and 11c at the hERG channel with values of 2.6 +/- 2.4% and 1.6 +/- 2.0%, respectively, rendered them unsuitable for medical use. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.119