(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 {3,3-difluoro-1-[hydroxy-((S)-1-phenyl-ethylcarbamoyl)-methyl]-propyl}-amide | 669063-38-1

• 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 {3,3-difluoro-1-[hydroxy-((S)-1-phenyl-ethylcarbamoyl)-methyl]-propyl}-amide
• CAS: 669063-38-1
• 化学式: C₃₇H₅₁F₂N₇O₆
• 分子量: 727.852
• InChiKey: UFTDUXPEVLCVPU-UDMDKJJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.77
• 重原子数：
  52.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 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 {3,3-difluoro-1-[hydroxy-((S)-1-phenyl-ethylcarbamoyl)-methyl]-propyl}-amide 在 戴斯-马丁氧化剂 作用下， 生成 LY533549
  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：

  (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 ethyl ester 在 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 达卡巴嗪 作用下， 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 {3,3-difluoro-1-[hydroxy-((S)-1-phenyl-ethylcarbamoyl)-methyl]-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