5-bromo-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(phenylmethoxy)-3-pyridine carboxamide | 912454-36-5

• 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: 5-bromo-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(phenylmethoxy)-3-pyridine carboxamide
• 英文别名: 6-benzyloxy-5-bromo-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide；5-bromo-N-[(1R,2R)-2-hydroxycyclohexyl]-6-phenylmethoxypyridine-3-carboxamide
• CAS: 912454-36-5
• 化学式: C₁₉H₂₁BrN₂O₃
• 分子量: 405.291
• InChiKey: XWACDGUINBMTTI-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(phenylmethoxy)-3-pyridine carboxamide 、 4-氯苯硼酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以55%的产率得到5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(phenylmethoxy)-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：

  6-羟基烟酸 在 喹啉 、 溴 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 potassium hydroxide 、 三氯氧磷 作用下， 以 N,N-二甲基乙酰胺 、 二甲基亚砜 为溶剂， 反应 24.88h， 生成 5-bromo-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(phenylmethoxy)-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

• Pyridine-3-carboxamide derivatives as CB1 inverse agonists
  申请人：Hebeisen Paul

  公开号：US20060229326A1

  公开（公告）日：2006-10-12

  The present invention relates to compounds of the formula wherein X and 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, such as obesity.

  本发明涉及以下式中的化合物，其中X和R1至R8如描述和索赔中所定义，并且其药学上可接受的盐。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，如肥胖症。
• PYRIDINE-3-CARBOXAMIDE DERIVATIVES AS CB1 INVERSE AGONISTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1868999A1

  公开（公告）日：2007-12-26
• US7229999B2
  申请人：——

  公开号：US7229999B2

  公开（公告）日：2007-06-12
• [EN] PYRIDINE-3-CARBOXAMIDE DERIVATIVES AS CB1 INVERSE AGONISTS<br/>[FR] DERIVES DE PYRIDINE-3-CARBOXAMIDE UTILISES COMME AGONISTES INVERSES DES CB1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2006106054A1

  公开（公告）日：2006-10-12

  [EN] The present invention relates to compounds of the formula (I) wherein X and 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, such as obesity.
  [FR] L'invention concerne des composés de formule (I) dans laquelle X et R¹ à R⁸ sont tels que définis dans la description et les revendications et des sels de ceux-ci acceptables sur le plan pharmaceutique. Les composés sont utiles dans le traitement et/ou la prophylaxie de maladies associées à la modulation des récepteurs CB1, telle que l'obésité.