3-{2-chloro-7-hydroxy-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-5-oxo-4,5-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl}benzoic acid | 1272673-67-2

• 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: 3-{2-chloro-7-hydroxy-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-5-oxo-4,5-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl}benzoic acid
• 英文别名: 3-[2-chloro-7-hydroxy-1-[4-(2-hydroxy-3-methoxyphenyl)phenyl]-5-oxo-4H-pyrrolo[3,2-b]pyridin-6-yl]benzoic acid
• CAS: 1272673-67-2
• 化学式: C₂₇H₁₉ClN₂O₆
• 分子量: 502.911
• InChiKey: LOJXJNGGOBHABS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 3-acetamido-1H-pyrrole-2-carboxylate 在 吡啶 、 盐酸 、 N-氯代丁二酰亚胺 、 四(三苯基膦)钯 、 水 、 copper diacetate 、 双(三甲基硅烷基)氨基钾 、 1-羟基苯并三唑 、 caesium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 126.0h， 生成 3-{2-chloro-7-hydroxy-1-[2'-hydroxy-3'-(methyloxy)-4-biphenylyl]-5-oxo-4,5-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl}benzoic acid
  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-PYRIDINE DERIVATIVES AS ACTIVATORS OF AMPK<br/>[FR] DÉRIVÉS PYRROLO-PYRIDINE UTILISÉS COMME ACTIVATEURS DE L'AMPK
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011029855A1

  公开（公告）日：2011-03-17

  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.

  本发明涉及式(I)的吡咯吡啶酮化合物及其盐，含有它们的药物组合物以及它们在医学上的应用。具体而言，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。
• Discovery of Pyridones As Oral AMPK Direct Activators
  作者：Olivier Mirguet、Stéphane Sautet、Catherine-Anne Clément、Jérôme Toum、Frédéric Donche、Celine Marques、Emilie Rondet、Mathieu Pizzonero、Benjamin Beaufils、Yann Dudit、Pascal Huet、Lionel Trottet、Pascal Grondin、Jean-Marie Brusq、Eric Boursier、Yannick Saintillan、Edwige Nicodeme

  DOI：10.1021/ml400157g

  日期：2013.7.11

  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.