2-(6-bromopyridin-3-yl)-5-fluoro-1H-benzo[d]imidazole | 1438251-24-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(6-bromopyridin-3-yl)-5-fluoro-1H-benzo[d]imidazole
• 英文别名: 2-(6-bromopyridin-3-yl)-6-fluoro-1H-benzimidazole
• CAS: 1438251-24-1
• 化学式: C₁₂H₇BrFN₃
• 分子量: 292.11
• InChiKey: BFSYMNGNFNAABF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(6-bromopyridin-3-yl)-5-fluoro-1H-benzo[d]imidazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 cis-4-{[5-(5-fluoro-1H-benzimidazol-2-yl)-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
• 作为产物：
  描述：

  4-氟-1,2-苯二胺 、 2-溴-5-醛基吡啶 在 potassium peroxymonosulfate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以91%的产率得到2-(6-bromopyridin-3-yl)-5-fluoro-1H-benzo[d]imidazole
  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

文献信息

• [EN] IMIDAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'IMIDAZOLE
  申请人：MERCK SHARP & DOHME

  公开号：WO2013074387A1

  公开（公告）日：2013-05-23

  Disclosed herein are novel imidazole derivative compounds i.e., benzimidazole and aza-benzimidazole derivatives that act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperiipidemia, diabetes mellitus and obesity. Further disclosed are methods of treating various DGAT1 -related diseases, and the use of such imidazole compounds as described herein in the manufacture of a medicament for such treatment.

  本文披露了一种新型咪唑衍生物化合物，即苯并咪唑和氮杂苯并咪唑衍生物，其作为DGAT1抑制剂，并可用于预防、治疗或作为高脂血症、糖尿病和肥胖的治疗药物。进一步披露了治疗各种与DGAT1相关疾病的方法，以及将本文所述的咪唑化合物用于制造用于该治疗的药物的用途。
• Potent DGAT1 Inhibitors in the Benzimidazole Class with a Pyridyl-oxy-cyclohexanecarboxylic Acid Moiety
  作者：Shuwen He、Qingmei Hong、Zhong Lai、Zhicai Wu、Yang Yu、David W. Kim、Pauline C. Ting、Jeffrey T. Kuethe、Ginger X. Yang、Tianying Jian、Jian Liu、Deodial Guiadeen、Arto D. Krikorian、Donald M. Sperbeck、Lisa M. Sonatore、Judyann Wiltsie、Christine C. Chung、Jack T. Gibson、JeanMarie Lisnock、Beth A. Murphy、Judith N. Gorski、Jinqi Liu、Dunlu Chen、Xiaoli Chen、Michael Wolff、Sharon X. Tong、Maria Madeira、Bindhu V. Karanam、Dong-Ming Shen、James M. Balkovec、Shirly Pinto、Ravi P. Nargund、Robert J. DeVita

  DOI：10.1021/ml400168h

  日期：2013.8.8

  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.