trans-4-[(5-formyl-2,3'-bipyridin-6'-yl)oxy]cyclohexanecarboxylic acid | 1442646-27-6

• 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: trans-4-[(5-formyl-2,3'-bipyridin-6'-yl)oxy]cyclohexanecarboxylic acid
• CAS: 1442646-27-6
• 化学式: C₁₈H₁₈N₂O₄
• 分子量: 326.352
• InChiKey: OPLVVRKLAUSUAT-CTYIDZIISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  89.38
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-氟-1,2-苯二胺 、 trans-4-[(5-formyl-2,3'-bipyridin-6'-yl)oxy]cyclohexanecarboxylic acid 在 potassium peroxymonosulfate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (1r,4r)-4-((5-(5-fluoro-1H-benzo[d]imidazol-2-yl)-[2,3'-bipyridin]-6'-yl)oxy)cyclohexane-1-carboxylic acid
  参考文献：
  名称：

  Potent DGAT1 Inhibitors in the Benzimidazole Class with a Pyridyl-oxy-cyclohexanecarboxylic Acid Moiety

  摘要：

  We report the design and synthesis of a series of novel DGAT1 inhibitors in the benzimidazole class with a pyridyl-oxy-cyclohexanecarboxylic acid moiety. In particular, compound 11A is a potent DGAT1 inhibitor with excellent selectivity against ACAT1. Compound 11A significantly reduces triglyceride excursion in lipid tolerance tests (LTT) in both mice and dogs at low plasma exposure. An in vivo study in mice with des-fluoro analogue 10A indicates that this series of compounds appears to distribute in intestine preferentially over plasma. The propensity to target intestine over plasma could be advantageous in reducing potential side effects since lower circulating levels of drug are required for efficacy. However, in the preclinical species, compound 11A undergoes cis/trans epimerization in vivo, which could complicate further development due to the presence of an active metabolite.

  DOI：

  10.1021/ml400168h
• 作为产物：
  描述：

  2-溴-5-醛基吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 potassium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 trans-4-[(5-formyl-2,3'-bipyridin-6'-yl)oxy]cyclohexanecarboxylic acid
  参考文献：
  名称：

  Potent DGAT1 Inhibitors in the Benzimidazole Class with a Pyridyl-oxy-cyclohexanecarboxylic Acid Moiety

  摘要：

  We report the design and synthesis of a series of novel DGAT1 inhibitors in the benzimidazole class with a pyridyl-oxy-cyclohexanecarboxylic acid moiety. In particular, compound 11A is a potent DGAT1 inhibitor with excellent selectivity against ACAT1. Compound 11A significantly reduces triglyceride excursion in lipid tolerance tests (LTT) in both mice and dogs at low plasma exposure. An in vivo study in mice with des-fluoro analogue 10A indicates that this series of compounds appears to distribute in intestine preferentially over plasma. The propensity to target intestine over plasma could be advantageous in reducing potential side effects since lower circulating levels of drug are required for efficacy. However, in the preclinical species, compound 11A undergoes cis/trans epimerization in vivo, which could complicate further development due to the presence of an active metabolite.

  DOI：

  10.1021/ml400168h