ethyl 5-chloro-3-[(cyanoacetyl)amino]-1-(4'-methyl-4-biphenylyl)-1H-pyrrole-2-carboxylate | 1438835-21-2

• 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: ethyl 5-chloro-3-[(cyanoacetyl)amino]-1-(4'-methyl-4-biphenylyl)-1H-pyrrole-2-carboxylate
• CAS: 1438835-21-2
• 化学式: C₂₃H₂₀ClN₃O₃
• 分子量: 421.883
• InChiKey: RLAQQHMMGFZRCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  84.12
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 5-chloro-3-[(cyanoacetyl)amino]-1-(4'-methyl-4-biphenylyl)-1H-pyrrole-2-carboxylate 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 0.03h， 以89%的产率得到2-chloro-7-hydroxy-1-(4'-methyl-4-biphenylyl)-5-oxo-4,5-dihydro-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile
  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：

  4-溴苯硼酸 在 吡啶 、 盐酸 、 N-氯代丁二酰亚胺 、 四(三苯基膦)钯 、 水 、 copper diacetate 、 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 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 116.5h， 生成 ethyl 5-chloro-3-[(cyanoacetyl)amino]-1-(4'-methyl-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