3-(6-氯-1H-苯并咪唑基-2-基)-丙酸 | 82138-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 3-(6-氯-1H-苯并咪唑基-2-基)-丙酸
• 英文名称: 3-(5-chloro-1H-benzo[d]imidazol-2-yl)propanoic acid
• 英文别名: 3-(5-chloro-1(3)H-benzimidazol-2-yl)-propionic acid；3-(5-Chlor-1(3)H-benzimidazol-2-yl)-propionsaeure；3-(6-Chloro-1H-benzoimidazol-2-yl)-propionic acid；3-(6-chloro-1H-benzimidazol-2-yl)propanoic acid
• CAS: 82138-56-5
• 化学式: C₁₀H₉ClN₂O₂
• mdl: MFCD06753442
• 分子量: 224.647
• InChiKey: LPODEKMPICKOID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  3-(6-氯-1H-苯并咪唑基-2-基)-丙酸 在 盐酸 、 sodium hydroxide 、 盐酸羟胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 21.0h， 生成 N-hydroxy-3-(1H-5-chlorobenzimidazol-2-yl)-propionamide
  参考文献：
  名称：

  Gunes; Cosar, Arzneimittel-Forschung/Drug Research, 1992, vol. 42, # 8, p. 1045 - 1048

  摘要：

  DOI：
• 作为产物：
  描述：

  在 溶剂黄146 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 3-(6-氯-1H-苯并咪唑基-2-基)-丙酸
  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

• 314. Structure and antimalarial activity. Part IV. Benziminazoles and mercaptodihydroglyoxalines
  作者：A. T. James、E. E. Turner

  DOI：10.1039/jr9500001515

  日期：——
• Lettre et al., Chemische Berichte, 1951, vol. 84, p. 719,727
  作者：Lettre et al.

  DOI：——

  日期：——
• MATSUMURA, SINGO;EHNOMOTO, XIROSI;ODZAKI, MASAKUNI;MORITA, IVAO;TODA, SIN+
  作者：MATSUMURA, SINGO、EHNOMOTO, XIROSI、ODZAKI, MASAKUNI、MORITA, IVAO、TODA, SIN+

  DOI：——

  日期：——
• JPS5731617A
  申请人：——

  公开号：JPS5731617A

  公开（公告）日：1982-02-20
• Hit-to-Lead Optimization and Discovery of 5-((5-([1,1′-Biphenyl]-4-yl)-6-chloro-1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase
  作者：Ping Lan、F. Anthony Romero、Dariusz Wodka、Andrew J. Kassick、Qun Dang、Tony Gibson、Daniel Cashion、Gaochao Zhou、Yuli Chen、Xiaoping Zhang、Aihua Zhang、Ying Li、Maria E. Trujillo、Qing Shao、Margaret Wu、Shiyao Xu、Huaibing He、Deidre MacKenna、Jocelyn Staunton、Kevin T. Chapman、Ann Weber、Iyassu K. Sebhat、Gergely M. Makara

  DOI：10.1021/acs.jmedchem.7b01344

  日期：2017.11.9

  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.