(1S,3aR,6aS)-2-((S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-butyl]-amide | 402958-31-0

• 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-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-butyl]-amide
• CAS: 402958-31-0
• 化学式: C₃₂H₄₉N₇O₆
• 分子量: 627.784
• InChiKey: JZPPXHZDNTXNFI-NTQJHLCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.92
• 重原子数：
  45.0
• 可旋转键数：
  14.0
• 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-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-butyl]-amide 在 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 为溶剂， 生成 (1S,3aR,6aS)-2-((S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid (1-cyclopropylaminooxalyl-butyl)-amide
  参考文献：
  名称：

  Discovery of a novel bicycloproline P2 bearing peptidyl α-ketoamide LY514962 as HCV protease inhibitor

  摘要：

  We describe herein the design, syntheses and evaluation of a number of bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme potency, enzyme selectivity, cellular activity and favorable ADME profiles. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.074
• 作为产物：
  描述：

  特拉匹伟/VX950中间体1 在 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 为溶剂， 生成 (1S,3aR,6aS)-2-((S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-butyl]-amide
  参考文献：
  名称：

  Discovery of a novel bicycloproline P2 bearing peptidyl α-ketoamide LY514962 as HCV protease inhibitor

  摘要：

  We describe herein the design, syntheses and evaluation of a number of bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme potency, enzyme selectivity, cellular activity and favorable ADME profiles. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.074

文献信息

• P1 and P3 optimization of novel bicycloproline P2 bearing tetrapeptidyl α-ketoamide based HCV protease inhibitors
  作者：Frantz Victor、Jason Lamar、Nancy Snyder、Yvonne Yip、Deqi Guo、Nathan Yumibe、Robert B. Johnson、Q.May Wang、John I. Glass、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2003.09.075

  日期：2004.1

  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.