methyl 5-[(6-chloro-5-iodo-1-{[2-(trimethylsilyl)ethoxy]-methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate | 1219741-39-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-[(6-chloro-5-iodo-1-{[2-(trimethylsilyl)ethoxy]-methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate
• 英文别名: methyl 5-((6-chloro-5-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoate；Methyl 5-[6-chloro-5-iodo-1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]oxy-2-methylbenzoate
• CAS: 1219741-39-5
• 化学式: C₂₂H₂₆ClIN₂O₄Si
• 分子量: 572.902
• InChiKey: HBMLQVNJWZCSHN-UHFFFAOYSA-N

物化性质

• 沸点：
  591.6±60.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.49
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-[(6-chloro-5-iodo-1-{[2-(trimethylsilyl)ethoxy]-methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate 在 草酰氯 、 水 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 30.17h， 生成 C₂₁H₂₄ClIN₆O₃Si
  参考文献：
  名称：

  [EN] BENZIMIDAZOLE DIRECT AMPK ACTIVATORS
  [FR] BENZIMIDAZOLE ACTIVATEURS DIRECT DE L'AMPK

  摘要：

  揭示了苯并咪唑化合物，以及其药物组合物和使用方法。其中一种实施方式是具有结构式（I）的化合物及其药用可接受的盐、前药和N-氧化物（以及其溶剂和水合物），其中R1、R2、R3、R4、Y和X如本文所述。在某些实施方式中，本文披露的化合物可以激活AMPK，并可用于通过激活AMPK途径治疗疾病。

  公开号：

  WO2018035128A1
• 作为产物：
  描述：

  6-氯-5-碘-2-(甲硫基)-1H-苯并[D]咪唑 在 potassium carbonate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.17h， 生成 methyl 5-[(6-chloro-5-iodo-1-{[2-(trimethylsilyl)ethoxy]-methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate
  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。
• [EN] NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS<br/>[FR] NOUVEAUX DÉRIVÉS DE BENZIMIDAZOLE CYCLIQUES UTILES COMME AGENTS ANTI-DIABÉTIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2010047982A1

  公开（公告）日：2010-04-29

  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。
• [EN] AMPK ACTIVATORS<br/>[FR] ACTIVATEURS DE L'AMPK
  申请人：[en]KALLYOPE, INC.

  公开号：WO2023097187A1

  公开（公告）日：2023-06-01

  This disclosure is directed, at least in part, to AMPK activators useful for the treatment of conditions or disorders associated with AMPK. In some embodiments, the condition or disorder is associated with the gut-brain axis. In some embodiments, condition or disorder is associated with systemic infection and inflammation from having a leaky gut barrier. In some embodiments, the AMPK activators are gut-restricted compounds. In some embodiments, the AMPK activators are agonists, super agonists, full agonists, or partial agonists.