(2R)-1-[(2R)-1-[(2R)-2-[[(2R,3R)-2-[[(2S)-2-[(1R)-1-hydroxy-2-[(2R)-pyrrolidin-2-yl]ethyl]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide

• 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: (2R)-1-[(2R)-1-[(2R)-2-[[(2R,3R)-2-[[(2S)-2-[(1R)-1-hydroxy-2-[(2R)-pyrrolidin-2-yl]ethyl]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide
• 化学式: C₃₃H₅₈N₆O₆
• 分子量: 634.86
• InChiKey: MRKGKMGWEHUWQN-VIDHWKOLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  45
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  174
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R)-1-[(2R)-1-[(2R)-2-[[(2R,3R)-2-[[(2S)-2-[(1R)-1-hydroxy-2-[(2R)-pyrrolidin-2-yl]ethyl]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide 、 异氰酸苄酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以25 mg的产率得到(2R)-N-benzyl-2-[(2R,3S)-3-[[(2R,3R)-1-[[(2R)-1-[(2R)-2-[(2R)-2-carbamoylpyrrolidine-1-carbonyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]-2-hydroxy-5-methylhexyl]pyrrolidine-1-carboxamide
  参考文献：
  名称：

  Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster

  摘要：

  Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile site substituent were synthesized. Inhibitory activities of the new inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.02.019
• 作为产物：
  描述：

  在 三氟乙酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (2R)-1-[(2R)-1-[(2R)-2-[[(2R,3R)-2-[[(2S)-2-[(1R)-1-hydroxy-2-[(2R)-pyrrolidin-2-yl]ethyl]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster

  摘要：

  Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile site substituent were synthesized. Inhibitory activities of the new inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.02.019

文献信息

• Effect of prime-site sequence of retro-inverso-modified HTLV-1 protease inhibitor
  作者：Chiyuki Awahara、Tadashi Tatsumi、Saki Furuta、Gen Shinjoh、Hiroyuki Konno、Kazuto Nosaka、Kazuya Kobayashi、Yasunao Hattori、Kenichi Akaji

  DOI：10.1016/j.bmc.2014.02.050

  日期：2014.4

  The effects of additional substituents covering the prime-site of retro-inverso (RI)-modified HTLV-1 protease inhibitors containing a hydroxyethylamine isoster were clarified. Stereo-selective construction of the most potent isoster backbone was achieved by the Evans-aldol reaction. Addition of N-acetylated D-amino acid corresponding to the P-2(1) site gave an RI-modified inhibitor showing superior inhibitory activity to the previous inhibitor. Inhibitory activities of the newly synthesized inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor. (C) 2014 Elsevier Ltd. All rights reserved.
• Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster
  作者：Tadashi Tatsumi、Chiyuki Awahara、Hiromi Naka、Saburo Aimoto、Hiroyuki Konno、Kazuto Nosaka、Kenichi Akaji

  DOI：10.1016/j.bmc.2010.02.019

  日期：2010.4

  Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile site substituent were synthesized. Inhibitory activities of the new inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.