3-羟基-3-甲基吡咯烷-1-羧酸苄酯 | 1262409-80-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-羟基-3-甲基吡咯烷-1-羧酸苄酯
• 英文名称: rac-benzyl (S)-3-hydroxy-3-methylpyrrolidine-1-carboxylate
• 英文别名: Benzyl 3-hydroxy-3-methylpyrrolidine-1-carboxylate；benzyl 3-hydroxy-3-methylpyrrolidine-1-carboxylate
• CAS: 1262409-80-2
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: NNPKZONNGQHEFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-羟基-3-甲基吡咯烷-1-羧酸苄酯 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 60.0 ℃ 、206.85 kPa 条件下， 反应 25.0h， 生成 (S)-2-(3-hydroxy-3-methylpyrrolidin-1-yl)-6-(4-(2-hydroxyethyl)piperazin-1-yl)-4-(trifluoromethyl)nicotinonitrile
  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：

  甲基溴化镁 、 N-Cbz-3-吡咯烷酮 以 四氢呋喃 、 乙醚 为溶剂， 生成 3-羟基-3-甲基吡咯烷-1-羧酸苄酯
  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.