5-((6-chloro-5-(phenylethynyl)-1H-benzo[d]imidazol-2-yl)-oxy)-2-methylbenzoic acid | 1219737-54-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-((6-chloro-5-(phenylethynyl)-1H-benzo[d]imidazol-2-yl)-oxy)-2-methylbenzoic acid
• 英文别名: 6-(6-chloro-5-phenylethynyl-1H-benzoimidazol-2-yloxy)-2-methyl-benzoic acid；5-[[5-chloro-6-(2-phenylethynyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid
• CAS: 1219737-54-8
• 化学式: C₂₃H₁₅ClN₂O₃
• 分子量: 402.837
• InChiKey: PDRSUSNUEHCSFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 5-[[5-chloro-6-(2-phenylethynyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoate 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以36 mg的产率得到5-((6-chloro-5-(phenylethynyl)-1H-benzo[d]imidazol-2-yl)-oxy)-2-methylbenzoic 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

• NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL AS ANTI-DIABETIC AGENTS
  申请人：BOOKSER BRETT C.

  公开号：US20100081643A1

  公开（公告）日：2010-04-01

  Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

  结构式（I）的新化合物是AMP-蛋白激酶的激活剂，并且在治疗、预防和抑制由AMPK激活的蛋白激酶介导的疾病方面非常有用。本发明的化合物在治疗2型糖尿病、高血糖、代谢综合征、肥胖、高胆固醇血症和高血压方面非常有用。
• US8394969B2
  申请人：——

  公开号：US8394969B2

  公开（公告）日：2013-03-12