3-氨基-5-乙基-1H-吡咯-2-羧酸乙酯 | 1194374-72-5

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 3-氨基-5-乙基-1H-吡咯-2-羧酸乙酯
• 英文名称: ethyl 3-amino-5-ethyl-1H-pyrrole-2-carboxylate
• CAS: 1194374-72-5
• 化学式: C₉H₁₄N₂O₂
• mdl: MFCD11111536
• 分子量: 182.222
• InChiKey: YVRLPBNXXIMQMY-UHFFFAOYSA-N

物化性质

• 沸点：
  337.0±42.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  68.1
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-氨基-5-乙基-1H-吡咯-2-羧酸乙酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 7-氯-2-乙基-5-(三氟甲基)-1H-吡咯并[3,2-b]吡啶-6-甲腈
  参考文献：
  名称：

  Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)

  摘要：

  Increased fructose consumption and its subsequent Metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, identification of a selective. KHK inhibitor may help to further elucidate the effect of KHK inhibition on these metabolic disorders. Until now, studies on KHK inhibition with small molecules have been limited due to the lack of viable in vivo pharmacological tools. Herein we report the discovery of 12, a selective KHK inhibitor with potency and properties suitable for evaluating KHK inhibition in rat models. Key structural features interacting with KHK were discovered through fragment-based screening and subsequent optimization using structure-based drug design, and parallel medicinal chemistry led to the identification of pyridine 12.

  DOI：

  10.1021/acs.jmedchem.7b00947
• 作为产物：
  描述：

  pent-2-ynenitrile 、 氨基丙二酸二乙酯盐酸盐 在 sodium 作用下， 以 乙醇 、 乙醚 为溶剂， 反应 4.5h， 以15%的产率得到3-氨基-5-乙基-1H-吡咯-2-羧酸乙酯
  参考文献：
  名称：

  Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)

  摘要：

  Increased fructose consumption and its subsequent Metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, identification of a selective. KHK inhibitor may help to further elucidate the effect of KHK inhibition on these metabolic disorders. Until now, studies on KHK inhibition with small molecules have been limited due to the lack of viable in vivo pharmacological tools. Herein we report the discovery of 12, a selective KHK inhibitor with potency and properties suitable for evaluating KHK inhibition in rat models. Key structural features interacting with KHK were discovered through fragment-based screening and subsequent optimization using structure-based drug design, and parallel medicinal chemistry led to the identification of pyridine 12.

  DOI：

  10.1021/acs.jmedchem.7b00947

文献信息

• Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)
  作者：Kim Huard、Kay Ahn、Paul Amor、David A. Beebe、Kris A. Borzilleri、Boris A. Chrunyk、Steven B. Coffey、Yang Cong、Edward L. Conn、Jeffrey S. Culp、Matthew S. Dowling、Matthew F. Gorgoglione、Jemy A. Gutierrez、John D. Knafels、Erik A. Lachapelle、Jayvardhan Pandit、Kevin D. Parris、Sylvie Perez、Jeffrey A. Pfefferkorn、David A. Price、Brian Raymer、Trenton T. Ross、Andre Shavnya、Aaron C. Smith、Timothy A. Subashi、Gregory J. Tesz、Benjamin A. Thuma、Meihua Tu、John D. Weaver、Yan Weng、Jane M. Withka、Gang Xing、Thomas V. Magee

  DOI：10.1021/acs.jmedchem.7b00947

  日期：2017.9.28

  Increased fructose consumption and its subsequent Metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, identification of a selective. KHK inhibitor may help to further elucidate the effect of KHK inhibition on these metabolic disorders. Until now, studies on KHK inhibition with small molecules have been limited due to the lack of viable in vivo pharmacological tools. Herein we report the discovery of 12, a selective KHK inhibitor with potency and properties suitable for evaluating KHK inhibition in rat models. Key structural features interacting with KHK were discovered through fragment-based screening and subsequent optimization using structure-based drug design, and parallel medicinal chemistry led to the identification of pyridine 12.