6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyridinecarboxylic acid | 1364677-94-0

• 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-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyridinecarboxylic acid
• 英文别名: 6-(4-chloro-phenyl)-5-cyclopropylmethoxy-pyridine-2-carboxylic acid；6-(4-chlorophenyl)-5-(cyclopropylmethoxy)pyridine-2-carboxylic acid
• CAS: 1364677-94-0
• 化学式: C₁₆H₁₄ClNO₃
• 分子量: 303.745
• InChiKey: KNIPTWZOFFXGRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyridinecarboxylic acid 、 (1R,2R)-2-氨基环己醇盐酸盐 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以73%的产率得到6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-N-[(1R,2R)-2-hydroxycyclohexyl]-2-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：

  2-氯-3-氟吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 乙醇 、 双氧水 、 sodium hydride 、 sodium carbonate 、 溶剂黄146 、 三乙胺 、 乙酰氯 、 二甲氨基甲酰氯 作用下， 以 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 mineral oil 为溶剂， 反应 65.58h， 生成 6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyridinecarboxylic acid
  参考文献：
  名称：

  HETEROARYLMETHYL AMIDES

  摘要：

  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。

  公开号：

  US20120065212A1

文献信息

• [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。
• [EN] 5,6-DISUBSTITUTED PYRIDINE-2-CARBOXAMIDES AS CANNABINOID RECEPTOR AGONISTS<br/>[FR] PYRIDINE-2-CARBOXAMIDES BISUBSTITUÉS EN 5,6 SERVANT D'AGONISTES DU RÉCEPTEUR CANNABINOÏDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015150438A1

  公开（公告）日：2015-10-08

  The invention relates to a compound of formula (I) wherein R1 to R4 are defined as in the description and in the claims. The compound of formula (I) are agonists of the Cannabinoid Receptor 2 and are therefore useful in the treatment of various diseases such as pain, atherosclerosis, inflammation etc.

  该发明涉及公式（I）的化合物，其中R1至R4的定义如描述和索赔中所述。公式（I）的化合物是大麻素受体2的激动剂，因此在治疗各种疾病如疼痛、动脉硬化、炎症等方面具有用处。
• Heteroarylmethyl amides
  申请人：Hoffman-La Roche Inc.

  公开号：US09090599B2

  公开（公告）日：2015-07-28

  The present invention relates to compounds of the formula 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.

  本发明涉及以下式子的化合物：其中A1，A2，A3和R1至R8在描述中有定义，并且其药学上可接受的盐、其制造、包含它们的制药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使用，例如特别是脂质代谢异常、动脉硬化和心血管疾病。
• 5,6-DISUBSTITUTED PYRIDINE-2-CARBOXAMIDES AS CANNABINOID RECEPTOR AGONISTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3126349A1

  公开（公告）日：2017-02-08
• NOVEL PYRIDINE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160376237A1

  公开（公告）日：2016-12-29

  The invention relates to a compound of formula (I) wherein R 1 to R 4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.