2-((5,6-dichloro-1H-benzo[d]imidazol-2-yl)thio)acetic acid | 5450-29-3

• 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-((5,6-dichloro-1H-benzo[d]imidazol-2-yl)thio)acetic acid
• 英文别名: (5,6-dichloro-1H-benzimidazol-2-ylmercapto)-acetic acid；(5,6-Dichlor-1H-benzimidazol-2-ylmercapto)-essigsaeure；[(5,6-Dichloro-1h-benzimidazol-2-yl)sulfanyl]acetic acid；2-[(5,6-dichloro-1H-benzimidazol-2-yl)sulfanyl]acetic acid
• CAS: 5450-29-3
• 化学式: C₉H₆Cl₂N₂O₂S
• 分子量: 277.131
• InChiKey: MDHUGAQJEKDLAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  91.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  溴乙酸 、 5,6-二氯苯并咪唑-2-硫醇 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 以50%的产率得到2-((5,6-dichloro-1H-benzo[d]imidazol-2-yl)thio)acetic acid
  参考文献：
  名称：

  Hit-to-Lead Optimization and Discovery of 5-((5-([1,1′-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase

  摘要：

  AMP-activated protein kinase (AMPK) plays an essential role as a cellular energy sensor and master regulator of metabolism in eukaryotes. Dysregulated lipid and carbohydrate metabolism resulting from insulin resistance leads to hyperglycemia, the hallmark of type 2 diabetes mellitus (T2DM). While pharmacological activation of AMPK is anticipated to improve these parameters, the discovery of selective, direct activators has proven challenging. We now describe a hit-to-lead effort resulting in the discovery of a potent and selective class of benzimidazole-based direct AMPK activators, exemplified by 5-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic acid, 42 (MK-3903). Compound 42 exhibited robust target engagement in mouse liver following oral dosing, leading to improved lipid metabolism and insulin sensitization in mice.

  DOI：

  10.1021/acs.jmedchem.7b01344

文献信息

• The Synthesis of Several Acid Analogs of 2-Mercaptobenzimidazole^1,2
  作者：Theodore L. Rebstock、Charles D. Ball、Charles L. Hamner、Harold M. Sell

  DOI：10.1021/ja01603a032

  日期：1956.11