6-chloro-5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-3-pyridine carboxamide | 1012792-57-2

• 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-5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-3-pyridine carboxamide
• 英文别名: 6-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide；6-chloro-5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]pyridine-3-carboxamide
• CAS: 1012792-57-2
• 化学式: C₁₈H₁₈Cl₂N₂O₂
• 分子量: 365.259
• InChiKey: IWSWAESQUCCIRU-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-3-pyridine carboxamide 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 palladium on activated charcoal 、 二乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0~120.0 ℃ 、40.0 kPa 条件下， 反应 0.42h， 生成 5-(4-chlorophenyl)-6-(2-cyclopropylethyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-3-pyridine carboxamide
  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
• 作为产物：
  描述：

  5-溴-6-羟基烟酸 在 喹啉 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 lithium hydroxide monohydrate 、 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 21.25h， 生成 6-chloro-5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-3-pyridine carboxamide
  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

• 3-Pyridinecarboxamide derivatives as HDL-cholesterol raising agents
  申请人：Andjelkovic Mirjana

  公开号：US20080085906A1

  公开（公告）日：2008-04-10

  The present invention relates to a method of raising HDL cholesterol comprising administering to a patient in need thereof a compound of the formula wherein A, G, R 1 to R 8 and R 17 are as defined in the description.

  本发明涉及一种提高HDL胆固醇的方法，包括向需要的患者施用以下公式的化合物： 其中A、G、R1至R8和R17如描述中所定义。
• 5-PHENYL-NICOTINAMIDE DERIVATIVES
  申请人：Hebeisen Paul

  公开号：US20080070931A1

  公开（公告）日：2008-03-20

  The present invention relates to compounds of the formula wherein R 1 to R 8 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors.

  本发明涉及公式中的化合物，其中R1至R8如描述和索赔中定义，并且其药用盐。这些化合物可用于治疗和/或预防与CB1受体调节相关的疾病。
• 5-phenyl-nicotinamide derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US07781593B2

  公开（公告）日：2010-08-24

  The present invention relates to compounds of the formula wherein R1 to R8 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors.

  本发明涉及式中的化合物，其中R1至R8如描述和权利要求中所定义，并且其药学上可接受的盐。该化合物对于治疗和/或预防与CB1受体调节相关的疾病是有用的。
• Pyrazinecarboxamide derivatives as HDL-cholesterol raising agents
  申请人：Hoffmann-La Roche Inc.

  公开号：US08188093B2

  公开（公告）日：2012-05-29

  The present invention relates to a method of raising HDL cholesterol comprising administering to a patient in need thereof a compound of the formula wherein A, G, R1 to R8 and R17 are as defined in the description.

  本发明涉及一种提高高密度脂蛋白胆固醇的方法，包括向需要的患者给予以下化合物的治疗，其化学式如下：其中A、G、R1至R8和R17的定义见说明书。
• 3-pyridinecarboxamide derivatives as HDL-cholesterol raising agents
  申请人：Hoffmann-La Roche Inc.

  公开号：US07812028B2

  公开（公告）日：2010-10-12

  The present invention relates to a method of raising HDL cholesterol comprising administering to a patient in need thereof a compound of the formula wherein A, G, R1 to R8 and R17 are as defined in the description.

  本发明涉及一种提高高密度脂蛋白胆固醇的方法，包括向需要的患者给予以下式子中的化合物：其中A、G、R1至R8和R17的定义见说明书。