ethyl 3-amino-5-chloro-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-1H-pyrrole-2-carboxylate | 1272674-58-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 3-amino-5-chloro-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-1H-pyrrole-2-carboxylate
• 英文别名: ethyl 3-amino-5-chloro-1-[4-(2-hydroxy-3-methoxyphenyl)phenyl]pyrrole-2-carboxylate
• CAS: 1272674-58-4
• 化学式: C₂₀H₁₉ClN₂O₄
• 分子量: 386.835
• InChiKey: JMARKHMGMRMPTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 3-amino-5-chloro-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-1H-pyrrole-2-carboxylate 在 吡啶 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-chloro-7-hydroxy-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-6-phenyl-1,4-dihydro-5H-pyrrolo[3,2-b]pyridin-5-one
  参考文献：
  名称：

  Discovery of Pyridones As Oral AMPK Direct Activators

  摘要：

  AMP-activated protein kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme that is activated in shortage of energy and suppressed in its surfeit. AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity, alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory changes. Thus, AMPK is a well-received therapeutic target for type 2 diabetes and other metabolic disorders. Here, we will report the discovery of pyrrolopyridone derivatives' as AMPK direct activators. We will illustrate the synthesis and structure activity relationships of the series as well as some pharmacokinetic results. Some compounds exhibited encouraging oral exposure and were evaluated in a mouse diabetic model Compound 17 showed oral activity at 30 mg/kg on blood glucose.

  DOI：

  10.1021/ml400157g
• 作为产物：
  描述：

  ethyl 3-(acetylamino)-1-(4-bromophenyl)-5-chloro-1H-pyrrole-2-carboxylate 在 盐酸 、 四(三苯基膦)钯 、 水 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 ethyl 3-amino-5-chloro-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  Discovery of Pyridones As Oral AMPK Direct Activators

  摘要：

  AMP-activated protein kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme that is activated in shortage of energy and suppressed in its surfeit. AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity, alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory changes. Thus, AMPK is a well-received therapeutic target for type 2 diabetes and other metabolic disorders. Here, we will report the discovery of pyrrolopyridone derivatives' as AMPK direct activators. We will illustrate the synthesis and structure activity relationships of the series as well as some pharmacokinetic results. Some compounds exhibited encouraging oral exposure and were evaluated in a mouse diabetic model Compound 17 showed oral activity at 30 mg/kg on blood glucose.

  DOI：

  10.1021/ml400157g

文献信息

• [EN] PYRROLO [3, 2 -D] PYRIMIDIN-3 -YL DERIVATIVES USED AS ACTIVATORS OF AMPK<br/>[FR] DÉRIVÉS PYRROLO [3,2-D] PYRIMIDIN-3-YLE UTILISÉS COMME ACTIVATEURS DE L'AMPK
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011138307A1

  公开（公告）日：2011-11-10

  The present invention relates to pyrrolopyrimidones compounds of the formula (I), salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds as activators of AMPK.

  本发明涉及式(I)的吡咯吡咪酮化合物及其盐，包含它们的药物组合物以及它们在医学上的应用。具体来说，本发明涉及化合物作为AMPK激活剂。
• PYRROLO-PYRIDINE DERIVATIVES AS ACTIVATORS OF AMPK
  申请人：Mirguet Olivier

  公开号：US20120172333A1

  公开（公告）日：2012-07-05

  The present invention relates to pyrrolopyridone compounds of the formula (I), salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds as activators of AMPK.

  本发明涉及公式（I）的吡咯吡啶酮化合物及其盐，包含它们的制药组合物以及它们在医学上的应用。特别地，本发明涉及作为AMPK激活剂的化合物。
• PYRROLO [3,2-D] PYRIMIDIN-3-YL DERIVATIVES USED AS ACTIVATORS OF AMPK
  申请人：Mirguet Olivier

  公开号：US20130053407A1

  公开（公告）日：2013-02-28

  Pyrrolopyrimidones compounds of the formula (I), salts thereof, and pharmaceutical compositions containing them are disclosed herein, as well as methods for their use in medicine, for instance as activators of AMPK.

  本文披露了式(I)的吡咯吡咪酮化合物及其盐以及含有它们的制药组合物，以及它们在医学上的使用方法，例如作为AMPK的激活剂。
• PYRROLO [3, 2 -D]PYRIMIDIN-3 -YL DERIVATIVES USED AS ACTIVATORS OF AMPK
  申请人：GlaxoSmithKline LLC

  公开号：EP2566868A1

  公开（公告）日：2013-03-13