pent-2-ynenitrile | 41727-21-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: pent-2-ynenitrile
• 英文别名: Pent-2-innitril；Pentynonitrile
• CAS: 41727-21-3
• 化学式: C₅H₅N
• 分子量: 79.1014
• InChiKey: XZJKVEKIQIHCIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  101.5±23.0 °C(Predicted)
• 密度：
  0.901±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  pent-2-ynenitrile 在 sodium 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 methyl 3-((1-cyano-3,3,3-trifluoroprop-1-en-2-yl)amino)-5-ethyl-1H-pyrrole-2-carboxylate
  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：

  1-丁炔 、 氰酸苯酯 在 正丁基锂 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 2.0h， 生成 pent-2-ynenitrile
  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

• Listemann, Mark L.; Schrock, Richard R., Organometallics, 1985, vol. 4, # 1, p. 74 - 83
  作者：Listemann, Mark L.、Schrock, Richard R.

  DOI：——

  日期：——
• van der Welle,R.A.; Brandsma,L., Recueil des Travaux Chimiques des Pays-Bas, 1973, vol. 92, p. 667 - 672
  作者：van der Welle,R.A.、Brandsma,L.

  DOI：——

  日期：——
• WESTMIJZE H.; KLEIJN H.; VERMEER P., SYNTHESIS, 1979, NO 6, 430-431
  作者：WESTMIJZE H.、 KLEIJN H.、 VERMEER P.

  DOI：——

  日期：——
• 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.