2-((6-chloro-5-(phenylethynyl)-1H-benzo[d]-imidazol-2-yl)thio)acetic acid | 1224839-93-3

• 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-((6-chloro-5-(phenylethynyl)-1H-benzo[d]-imidazol-2-yl)thio)acetic acid
• 英文别名: (6-chloro-5-phenylethynyl-1H-benzoimidazol-2-ylsulfanyl)-acetic acid；2-[[5-chloro-6-(2-phenylethynyl)-1H-benzimidazol-2-yl]sulfanyl]acetic acid
• CAS: 1224839-93-3
• 化学式: C₁₇H₁₁ClN₂O₂S
• 分子量: 342.806
• InChiKey: CEJANWVTUAVULS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  在 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.0h， 以2.4 mg的产率得到2-((6-chloro-5-(phenylethynyl)-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

• [EN] NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS<br/>[FR] NOUVEAUX AGENTS ANTIDIABÉTIQUES UTILES AVEC DES DÉRIVÉS DE BENZIMIDAZOLE CYCLIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2010051176A1

  公开（公告）日：2010-05-06

  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，可用于治疗、预防和抑制由AMPK激活的蛋白激酶介导的疾病。本发明的化合物对于治疗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是有用的。
• NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL AS ANTI-DIABETIC AGENTS
  申请人：Dang Qun

  公开号：US20110195964A1

  公开（公告）日：2011-08-11

  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，可用于治疗、预防和抑制由AMPK激活的蛋白激酶介导的疾病。本发明的化合物可用于治疗2型糖尿病、高血糖、代谢综合征、肥胖症、高胆固醇血症和高血压。
• Cyclic benzimidazole derivatives useful as anti-diabetic agents
  申请人：Dang Qun

  公开号：US08563746B2

  公开（公告）日：2013-10-22

  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，并且可用于治疗、预防和抑制由AMPK激活的蛋白激酶介导的疾病。本发明的化合物可用于治疗2型糖尿病、高血糖、代谢综合征、肥胖症、高胆固醇血症和高血压。
• NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2352374A1

  公开（公告）日：2011-08-10
• US8563746B2
  申请人：——

  公开号：US8563746B2

  公开（公告）日：2013-10-22