(S)-2-(5-chloro-4-(methylsulfonyl)-2-oxopyridin-1(2H)-yl)-3-cyclopentyl-N-(5-methylpyridin-2-yl)propanamide | 1174013-29-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (S)-2-(5-chloro-4-(methylsulfonyl)-2-oxopyridin-1(2H)-yl)-3-cyclopentyl-N-(5-methylpyridin-2-yl)propanamide
• 英文别名: (2S)-2-(5-chloro-4-methylsulfonyl-2-oxopyridin-1-yl)-3-cyclopentyl-N-(5-methylpyridin-2-yl)propanamide
• CAS: 1174013-29-6
• 化学式: C₂₀H₂₄ClN₃O₄S
• 分子量: 437.947
• InChiKey: VTOVFAJFDHFMSW-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-5-甲基吡啶 、 methyl (S)-2-(5-chloro-4-(methylsulfonyl)-2-oxopyridin-1(2H)-yl)-3-cyclopentylpropanoate 在 二甲基氯化铝 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 3.0h， 以73%的产率得到(S)-2-(5-chloro-4-(methylsulfonyl)-2-oxopyridin-1(2H)-yl)-3-cyclopentyl-N-(5-methylpyridin-2-yl)propanamide
  参考文献：
  名称：

  Pyridones as glucokinase activators: Identification of a unique metabolic liability of the 4-sulfonyl-2-pyridone heterocycle

  摘要：

  A promising area of novel anti-diabetic therapy involves identification of small molecule activators of the glucokinase enzyme to reduce blood glucose and normalize glucose stimulated insulin secretion. Herein, we report the identification and optimization of a series of 4-sulfonyl-2-pyridone activators. The activators were evaluated for in vitro biochemical activation and pharmacokinetic properties. As part of these efforts, a unique metabolic liability of the 4-sulfonyl-2-pyridone ring system was identified wherein this heterocycle readily undergoes conjugation with glutathione under non-enzymatic conditions. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.107

文献信息

• Pyridones as glucokinase activators: Identification of a unique metabolic liability of the 4-sulfonyl-2-pyridone heterocycle
  作者：Jeffrey A. Pfefferkorn、Jihong Lou、Martha L. Minich、Kevin J. Filipski、Mingying He、Ru Zhou、Syed Ahmed、John Benbow、Angel-Guzman Perez、Meihua Tu、John Litchfield、Raman Sharma、Karen Metzler、Francis Bourbonais、Cong Huang、David A. Beebe、Peter J. Oates

  DOI：10.1016/j.bmcl.2009.04.107

  日期：2009.6

  A promising area of novel anti-diabetic therapy involves identification of small molecule activators of the glucokinase enzyme to reduce blood glucose and normalize glucose stimulated insulin secretion. Herein, we report the identification and optimization of a series of 4-sulfonyl-2-pyridone activators. The activators were evaluated for in vitro biochemical activation and pharmacokinetic properties. As part of these efforts, a unique metabolic liability of the 4-sulfonyl-2-pyridone ring system was identified wherein this heterocycle readily undergoes conjugation with glutathione under non-enzymatic conditions. (C) 2009 Elsevier Ltd. All rights reserved.