ethyl 3-acetamido-1-(4-ethylphenyl)-1H-pyrrole-2-carboxylate | 1272674-13-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: ethyl 3-acetamido-1-(4-ethylphenyl)-1H-pyrrole-2-carboxylate
• 英文别名: ethyl 3-(acetylamino)-1-(4-ethylphenyl)-1H-pyrrole-2-carboxylate；Ethyl 3-acetamido-1-(4-ethylphenyl)pyrrole-2-carboxylate；ethyl 3-acetamido-1-(4-ethylphenyl)pyrrole-2-carboxylate
• CAS: 1272674-13-1
• 化学式: C₁₇H₂₀N₂O₃
• 分子量: 300.357
• InChiKey: LFRJGXPTZMVRDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-acetamido-1-(4-ethylphenyl)-1H-pyrrole-2-carboxylate 在 N-氯代丁二酰亚胺 作用下， 以 四氢呋喃 为溶剂， 以77%的产率得到ethyl 3-(acetylamino)-5-chloro-1-(4-ethylphenyl)-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
• 作为产物：
  描述：

  ethyl 3-acetamido-1H-pyrrole-2-carboxylate 、 4-乙基苯硼酸 在 copper diacetate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以73%的产率得到ethyl 3-acetamido-1-(4-ethylphenyl)-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

• 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.