6-chloro-4-(4-chlorophenyl)-5-(2,2,2-trifluoroethoxy)-2-pyridinemethanol | 1364676-96-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-chloro-4-(4-chlorophenyl)-5-(2,2,2-trifluoroethoxy)-2-pyridinemethanol
• 英文别名: [6-chloro-4-(4-chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-methanol；[6-chloro-4-(4-chlorophenyl)-5-(2,2,2-trifluoroethoxy)-pyridin-2-yl]methanol；[6-chloro-4-(4-chlorophenyl)-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methanol；[6-Chloro-4-(4-chlorophenyl)-5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methanol
• CAS: 1364676-96-9
• 化学式: C₁₄H₁₀Cl₂F₃NO₂
• 分子量: 352.14
• InChiKey: XDLVHNWRWKPQRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  6-chloro-4-(4-chlorophenyl)-5-(2,2,2-trifluoroethoxy)-2-pyridinemethanol 在 sodium hypochlorite 、 sodium chlorite 、 2,2,6,6-四甲基哌啶氧化物 、 四甲基溴化铵 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 锌 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 38.0h， 生成 4-(4-chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid {(S)-2-[(E)-methoxyimino]-cyclohexyl}-amide
  参考文献：
  名称：

  [EN] OXIME COMPOUNDS AS HDL-CHOLESTEROL RAISING AGENTS
  [FR] COMPOSÉS D'OXIME EN TANT QU'AGENTS AUGMENTANT LE HDL-CHOLESTÉROL

  摘要：

  本发明涉及公式（I）中的化合物，其中A1至A3和R1至R9在描述中有定义，以及其药用盐，其制备方法，含有它们的药物组合物以及它们作为治疗和/或预防可用高密度脂蛋白胆固醇升高剂治疗的疾病的药物的用途，例如特别是脂质代谢异常，动脉粥样硬化和心血管疾病。

  公开号：

  WO2012080144A1
• 作为产物：
  描述：

  2-氯-6-羟基甲基吡啶-3-醇 在 六甲基磷酰三胺 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium hydride 、 碳酸氢钠 、 sodium carbonate 作用下， 以 水 、 甲苯 、 mineral oil 为溶剂， 反应 44.5h， 生成 6-chloro-4-(4-chlorophenyl)-5-(2,2,2-trifluoroethoxy)-2-pyridinemethanol
  参考文献：
  名称：

  6-Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds

  摘要：

  We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed.

  DOI：

  10.1021/jm4010708

文献信息

• HETEROARYLMETHYL AMIDES
  申请人：Hebeisen Paul

  公开号：US20120065212A1

  公开（公告）日：2012-03-15

  The present invention relates to compounds of the formula wherein A 1 , A 2 , A 3 and R 1 to R 8 are defined in the description, and to pharmaceutically acceptable salts thereof, their manufacture, pharmaceutical compositions containing them and their use as medicaments for the treatment and/or prophylaxis of diseases which can be treated with HDL-cholesterol raising agents, such as particularly dyslipidemia, atherosclerosis and cardiovascular diseases.

  本发明涉及以下公式的化合物，其中A1、A2、A3和R1至R8在描述中有定义，并且其药用盐，其制备，含有它们的药物组合物以及它们作为药物用于治疗和/或预防可用高密度脂蛋白胆固醇升高剂治疗的疾病，例如特别是血脂异常、动脉粥样硬化和心血管疾病。
• [EN] HETEROARYLMETHYL AMIDES<br/>[FR] HÉTÉROARYLMÉTHYL-AMIDES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012032018A1

  公开（公告）日：2012-03-15

  The present invention relates to compounds of the formula I wherein A1, A2, A3 and R1 to R8 are defined in the description, and to pharmaceutically acceptable salts thereof, their manufacture, pharmaceutical compositions containing them and their use as medicaments for the treatment and/or prophylaxis of diseases which can be treated with HDL-cholesterol raising agents, such as particularly dyslipidemia, atherosclerosis and cardiovascular diseases.

  本发明涉及公式I中的化合物，其中A1、A2、A3和R1至R8在描述中有定义，以及其药用盐，其制备方法，含有它们的药物组合物以及它们作为药物用于治疗和/或预防可以用HDL-胆固醇升高剂治疗的疾病，如特别是脂质代谢异常、动脉粥样硬化和心血管疾病。
• OXIME COMPOUNDS
  申请人：Hebeisen Paul

  公开号：US20120157476A1

  公开（公告）日：2012-06-21

  The present invention relates to compounds of the formula wherein A 1 to A 3 and R 1 to R 9 are defined in the description, and to pharmaceutically acceptable salts thereof, their manufacture, pharmaceutical compositions containing them and their use as medicaments for the treatment and/or prophylaxis of diseases which can be treated with HDL-cholesterol raising agents, such as particularly dyslipidemia, atherosclerosis and cardiovascular diseases.

  本发明涉及以下式中的化合物，其中A1至A3和R1至R9在描述中有定义，并且其药用盐，其制备方法，含有它们的药物组合物以及它们作为治疗和/或预防可用高密度脂蛋白胆固醇升高剂治疗的疾病的药物的用途，例如特别是脂质代谢异常，动脉粥样硬化和心血管疾病。
• OXIME COMPOUNDS AS HDL-CHOLESTEROL RAISING AGENTS
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2651895B1

  公开（公告）日：2015-07-01
• US8669254B2
  申请人：——

  公开号：US8669254B2

  公开（公告）日：2014-03-11