(1S,3aR,6aS)-2-((S)-3,3-Dimethyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-3,3-difluoro-propyl]-amide | 402958-45-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (1S,3aR,6aS)-2-((S)-3,3-Dimethyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-3,3-difluoro-propyl]-amide
• CAS: 402958-45-6
• 化学式: C₃₂H₄₇F₂N₇O₆
• 分子量: 663.765
• InChiKey: KEGLQKYGZUPPPR-SQFTWYIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  47.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  182.72
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (1S,3aR,6aS)-2-((S)-3,3-Dimethyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-3,3-difluoro-propyl]-amide 在 戴斯-马丁氧化剂 作用下， 生成 (3S,3aS,6aR)-N-[1-(cyclopropylamino)-5,5-difluoro-1,2-dioxopentan-3-yl]-2-[(2S)-3,3-dimethyl-2-[[(2S)-3-methyl-2-(pyrazine-2-carbonylamino)butanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide
  参考文献：
  名称：

  P1 and P3 optimization of novel bicycloproline P2 bearing tetrapeptidyl α-ketoamide based HCV protease inhibitors

  摘要：

  With the aim of discovering potent and selective HCV protease inhibitors, we synthesized and evaluated a series of Ia based tetrapeptidyl ketoamides with additional modification(s) at P1', P1, and P3 positions. As a result of this effort, we found that replacement of the P3 valine with tert-leucine resulted in the discovery of a series of inhibitors (e.g., 3a, 3c, and 4c) endowed with improved enzyme and/or cellular activity relative to Ia. When dosed to F-344 rats orally at 50 mg/kg, 3a achieved 2.5 x higher liver and plasma exposure in comparison to that detected with 1a. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.075
• 作为产物：
  描述：

  L-叔亮氨酸甲酯盐酸盐 在 palladium on activated charcoal sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 1-羟基苯并三唑 、 达卡巴嗪 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 为溶剂， 生成 (1S,3aR,6aS)-2-((S)-3,3-Dimethyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-3,3-difluoro-propyl]-amide
  参考文献：
  名称：

  P1 and P3 optimization of novel bicycloproline P2 bearing tetrapeptidyl α-ketoamide based HCV protease inhibitors

  摘要：

  With the aim of discovering potent and selective HCV protease inhibitors, we synthesized and evaluated a series of Ia based tetrapeptidyl ketoamides with additional modification(s) at P1', P1, and P3 positions. As a result of this effort, we found that replacement of the P3 valine with tert-leucine resulted in the discovery of a series of inhibitors (e.g., 3a, 3c, and 4c) endowed with improved enzyme and/or cellular activity relative to Ia. When dosed to F-344 rats orally at 50 mg/kg, 3a achieved 2.5 x higher liver and plasma exposure in comparison to that detected with 1a. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.075