(3′R,9′S)-9′-(tert-butyldimethylsilyloxy)-2-iodo-7′,7′-dimethyl-4′-(tetrahydro-2H-pyran-4-yl)-3′-(4-(trifluoromethyl)phenyl)-6′,7′,8′,9′-tetrahydro-3′H-spiro[cyclopentane-1,1′-furo[3,4-c]quinoline] | 1332488-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (3′R,9′S)-9′-(tert-butyldimethylsilyloxy)-2-iodo-7′,7′-dimethyl-4′-(tetrahydro-2H-pyran-4-yl)-3′-(4-(trifluoromethyl)phenyl)-6′,7′,8′,9′-tetrahydro-3′H-spiro[cyclopentane-1,1′-furo[3,4-c]quinoline]
• 英文别名: (3'R,9'S)-9'-(tert-butyldimethylsilyloxy)-2-iodo-7',7'-dimethyl-4'-(tetrahydro-2H-pyran-4-yl)-3'-(4-(trifluoromethyl)phenyl)-6',7',8',9'-tetrahydro-3'H-spiro[cyclopentane-1,1'-furo[3,4-c]quinoline]；tert-butyl-[(3R,9S)-2'-iodo-7,7-dimethyl-4-(oxan-4-yl)-3-[4-(trifluoromethyl)phenyl]spiro[3,6,8,9-tetrahydrofuro[3,4-c]quinoline-1,1'-cyclopentane]-9-yl]oxy-dimethylsilane
• CAS: 1332488-45-5
• 化学式: C₃₅H₄₇F₃INO₃Si
• 分子量: 741.748
• InChiKey: NFFCWZBSYWEFFW-REJDYQOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.33
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3′R,9′S)-9′-(tert-butyldimethylsilyloxy)-2-iodo-7′,7′-dimethyl-4′-(tetrahydro-2H-pyran-4-yl)-3′-(4-(trifluoromethyl)phenyl)-6′,7′,8′,9′-tetrahydro-3′H-spiro[cyclopentane-1,1′-furo[3,4-c]quinoline] 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 (3′R,9′S)-9′-(tert-butyldimethylsilyloxy)-7′,7′-dimethyl-4′-(tetrahydro-2H-pyran-4-yl)-3′-(4-(trifluoromethyl)phenyl)-6′,7′,8′,9′-tetrahydro-3′H-spiro[cyclopentane-1,1′-furo[3,4-c]quinoline]
  参考文献：
  名称：

  Potent Cholesteryl Ester Transfer Protein Inhibitors of Reduced Lipophilicity: 1,1′-Spiro-Substituted Hexahydrofuroquinoline Derivatives

  摘要：

  A series of 1,1'-spiro-substituted hexahydrofuroquinoline derivatives exhibiting potent cholesteryl ester transfer protein (CETP) inhibition at reduced lipophilicity was identified. A focused structure-activity relationship (SAR) exploration led to the potent and comparatively polar CETP inhibitor 26 showing robust high density lipoprotein-cholesterol (HDL-C) elevation and low density lipoprotein-cholesterol (LDL-C) reduction in transgenic hCETP/hApoB-100 mice. Compound 26 was also shown to positively differentiate from highly lipophilic CETP inhibitors in its complete elimination from fat tissue in hCETP transgenic mice as evident within 21 days after cessation of treatment. In addition, compound 26 showed no significant effects on aldosterone secretion from H295R cells, as well as no significant effects on blood pressure and electrocardiogram parameters in telemetrized cynomolgus monkeys.

  DOI：

  10.1021/jm500431d
• 作为产物：
  描述：

  (S)-ethyl 5-(tert-butyldimethylsilyloxy)-2,4-diiodo-7,7-dimethyl-5,6,7,8-tetrahydroquinoline-3-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 异丙基氯化镁 、 一氯化碘 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 cesium fluoride 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 98.0h， 生成 (3′R,9′S)-9′-(tert-butyldimethylsilyloxy)-2-iodo-7′,7′-dimethyl-4′-(tetrahydro-2H-pyran-4-yl)-3′-(4-(trifluoromethyl)phenyl)-6′,7′,8′,9′-tetrahydro-3′H-spiro[cyclopentane-1,1′-furo[3,4-c]quinoline]
  参考文献：
  名称：

  Potent Cholesteryl Ester Transfer Protein Inhibitors of Reduced Lipophilicity: 1,1′-Spiro-Substituted Hexahydrofuroquinoline Derivatives

  摘要：

  A series of 1,1'-spiro-substituted hexahydrofuroquinoline derivatives exhibiting potent cholesteryl ester transfer protein (CETP) inhibition at reduced lipophilicity was identified. A focused structure-activity relationship (SAR) exploration led to the potent and comparatively polar CETP inhibitor 26 showing robust high density lipoprotein-cholesterol (HDL-C) elevation and low density lipoprotein-cholesterol (LDL-C) reduction in transgenic hCETP/hApoB-100 mice. Compound 26 was also shown to positively differentiate from highly lipophilic CETP inhibitors in its complete elimination from fat tissue in hCETP transgenic mice as evident within 21 days after cessation of treatment. In addition, compound 26 showed no significant effects on aldosterone secretion from H295R cells, as well as no significant effects on blood pressure and electrocardiogram parameters in telemetrized cynomolgus monkeys.

  DOI：

  10.1021/jm500431d