(R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol | 1332486-56-2

• 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: (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol
• 英文别名: (R)-((5S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol；(R)-[(5S)-5-[tert-butyl(dimethyl)silyl]oxy-4-iodo-7,7-dimethyl-2-propan-2-yl-6,8-dihydro-5H-quinolin-3-yl]-[4-(trifluoromethyl)phenyl]methanol
• CAS: 1332486-56-2
• 化学式: C₂₈H₃₉F₃INO₂Si
• 分子量: 633.608
• InChiKey: WEOANDSLFDVQDD-NBGIEHNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.95
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  42.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium 10% on activated carbon 四丁基氟化铵 、 氢气 、 一氯化碘 、 三乙胺 、 cesium fluoride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0~50.0 ℃ 、1.0 MPa 条件下， 反应 84.0h， 生成 (3′R,9′S)-4′-isopropyl-7′,7′-dimethyl-3′-(4-(trifluoromethyl)phenyl)-6′,7′,8′,9′-tetrahydro-3′H-spiro[cyclopentane-1,1′-furo[3,4-c]quinolin]-9′-ol
  参考文献：
  名称：

  [EN] TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION
  [FR] DÉRIVÉS DE PYRIDINE TRICYCLIQUE, MÉDICAMENTS CONTENANT DE TELS COMPOSÉS, LEUR UTILISATION ET L'UN DE LEURS PROCÉDÉS DE SYNTHÈSE

  摘要：

  本发明涉及由式（I）定义的化合物，其中变量R1-R8如描述中所定义，具有有价值的药理活性。特别地，这些化合物是胆固醇酯转移蛋白（CETP）的抑制剂，因此适用于治疗和预防受该酶抑制影响的疾病。

  公开号：

  WO2012110599A1
• 作为产物：
  描述：

  ethyl 2,4-dichloro-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-3-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 2,6-二甲基吡啶 、 N,N-diethylaniline borane 、 (1R,2S)-1-氨基-2-茚醇 、 异丙基氯化镁 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 乙酰氯 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 86.58h， 生成 (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol
  参考文献：
  名称：

  [EN] TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION
  [FR] DÉRIVÉS TRICYCLIQUES DE PYRIDINE, MÉDICAMENTS CONTENANT LESDITS COMPOSÉS, UTILISATION ASSOCIÉE ET PROCÉDÉ DE PRÉPARATION ASSOCIÉE

  摘要：

  本发明涉及由式（I）定义的化合物，其中变量R1-R8如描述中所定义，具有有价值的药理活性。特别是，这些化合物是胆固醇酯转移蛋白（CETP）的抑制剂，因此适用于治疗和预防受该酶抑制影响的疾病。

  公开号：

  WO2011101424A1

文献信息

• TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION
  申请人：WAGNER Holger

  公开号：US20120046304A1

  公开（公告）日：2012-02-23

  The present invention relates to compounds defined by formula I wherein the variables R 1 -R 8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol ester transfer protein (CETP) and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme.

  本发明涉及由公式I定义的化合物 其中变量R1-R8定义如说明书中所述，具有宝贵的药理活性。特别是，这些化合物是胆固醇酯转移蛋白（CETP）的抑制剂，因此适合用于治疗和预防可以通过抑制该酶而影响的疾病。
• Tricyclic pyridine derivatives, medicaments containing such compounds, their use and process for their preparation
  申请人：Wagner Holger

  公开号：US20130053404A1

  公开（公告）日：2013-02-28

  The present invention relates to compounds defined by formula I wherein the variables R 1 -R 8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol ester transfer protein (CETP) and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme.

  本发明涉及由式I定义的化合物，其中变量R1-R8如描述中所定义，具有有价值的药理活性。特别地，这些化合物是胆固醇酯转移蛋白（CETP）的抑制剂，因此适用于治疗和预防受该酶抑制影响的疾病。
• [EN] CRYSTALLINE FORMS OF OCTAHYDRO-3H-SPIRO [FURO [3, 4-C] QUINOLINE -1, 4 '-PYRAN] -9-OL<br/>[FR] FORMES CRISTALLINES D'OCTAHYDRO-3H-SPIRO[FURO[3,4-C]QUINOLINE-1,4'-PYRANE]-9-OL
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013024149A1

  公开（公告）日：2013-02-21

  The present invention relates to crystalline forms of the compound of formula (I) as shown in the description and its hydrochloride or hydrobromide salts, to a process for the manufacture thereof, and to the use thereof in pharmaceutical compositions.

  本发明涉及公式（I）所示化合物的晶型，以及其盐，包括盐酸盐或溴化盐，以及其制备方法和在药物组合物中的用途。
• Crystalline forms of a hexahydrofuro[3,4-c]quinoline derivative
  申请人：OSTERMEIER Markus

  公开号：US20130210851A1

  公开（公告）日：2013-08-15

  The present invention relates to crystalline forms of (3R,9S)-4-isopropyl-7,7-dimethyl-3-(4-(trifluoromethyl)phenyl)-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran]-9-ol and its hydrochloride or hydrobromide salts, to a process for the manufacture thereof, and to the use thereof in pharmaceutical compositions.

  本发明涉及(3R,9S)-4-异丙基-7,7-二甲基-3-(4-(三氟甲基)苯基)-2′,3′,5′,6,6′,7,8,9-辛氢-3H-螺[furo[3,4-c]喹啉-1,4′-吡喃]-9-醇及其盐的晶型，以及其在制药组合物中的使用的制造方法。
• Potent Cholesteryl Ester Transfer Protein Inhibitors of Reduced Lipophilicity: 1,1′-Spiro-Substituted Hexahydrofuroquinoline Derivatives
  作者：Thomas Trieselmann、Holger Wagner、Klaus Fuchs、Dieter Hamprecht、Daniela Berta、Paolo Cremonesi、Rüdiger Streicher、Gerd Luippold、Astrid Volz、Michael Markert、Herbert Nar

  DOI：10.1021/jm500431d

  日期：2014.11.13

  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.