(2S)-3-cyclopentyl-N-(5-methylpyrazin-2-yl)-2-(3-methylsulfonyl-2-oxopyridin-1-yl)propanamide | 1254730-47-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (2S)-3-cyclopentyl-N-(5-methylpyrazin-2-yl)-2-(3-methylsulfonyl-2-oxopyridin-1-yl)propanamide
• CAS: 1254730-47-6
• 化学式: C₁₉H₂₄N₄O₄S
• 分子量: 404.49
• InChiKey: KBHLZFRBKWQBID-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-5-甲基吡嗪 、 methyl (S)-3-cyclopentyl-2-(3-(methylsulfonyl)-2-oxopyridin-1(2H)-yl)propanoate 在 三甲基铝 作用下， 以 1,2-二氯乙烷 、 甲苯 为溶剂， 生成 (2S)-3-cyclopentyl-N-(5-methylpyrazin-2-yl)-2-(3-methylsulfonyl-2-oxopyridin-1-yl)propanamide
  参考文献：
  名称：

  Intrinsic electrophilicity of the 4-methylsulfonyl-2-pyridone scaffold in glucokinase activators: Role of glutathione-S-transferases and in vivo quantitation of a glutathione conjugate in rats

  摘要：

  Previous studies on the in vitro metabolism of 4-alkylsulfonyl-2-pyridone-based glucokinase activators revealed a facile, non-enzymatic displacement of the 4-alkylsulfonyl group by glutathione. In the present studies, a role for glutathione-S-transferases (GST) as catalysts in the desulfonylation reaction was demonstrated using a combination of human liver microsomes, human liver cytosol and human GSTs. The identification of a glutathione conjugate in circulation following intravenous administration of a candidate 4-methylsulfonyl-2-pyridone to rats confirmed the relevance of the in vitro findings. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.095

文献信息

• Intrinsic electrophilicity of the 4-methylsulfonyl-2-pyridone scaffold in glucokinase activators: Role of glutathione-S-transferases and in vivo quantitation of a glutathione conjugate in rats
  作者：John Litchfield、Raman Sharma、Karen Atkinson、Kevin J. Filipski、Stephen W. Wright、Jeffrey A. Pfefferkorn、Beijing Tan、Rachel E. Kosa、Benjamin Stevens、Meihua Tu、Amit S. Kalgutkar

  DOI：10.1016/j.bmcl.2010.08.095

  日期：2010.11

  Previous studies on the in vitro metabolism of 4-alkylsulfonyl-2-pyridone-based glucokinase activators revealed a facile, non-enzymatic displacement of the 4-alkylsulfonyl group by glutathione. In the present studies, a role for glutathione-S-transferases (GST) as catalysts in the desulfonylation reaction was demonstrated using a combination of human liver microsomes, human liver cytosol and human GSTs. The identification of a glutathione conjugate in circulation following intravenous administration of a candidate 4-methylsulfonyl-2-pyridone to rats confirmed the relevance of the in vitro findings. (C) 2010 Elsevier Ltd. All rights reserved.