KNI-357

• 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: KNI-357
• 英文别名: N-[(1S,2S)-1-Benzyl-3-((R)-4-tert-butylcarbamoyl-thiazolidin-3-yl)-2-hydroxy-3-oxo-propyl]-succinamic acid；4-[[(2S,3S)-4-[(4R)-4-(tert-butylcarbamoyl)-1,3-thiazolidin-3-yl]-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-oxobutanoic acid
• 化学式: C₂₂H₃₁N₃O₆S
• 分子量: 465.571
• InChiKey: ZMHWWIZQCAPMQI-BXWFABGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  丁二酸酐 、 H-bAla(2S-OH,3S-Bn)-Thz-NHtBu.Cl- 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以88%的产率得到KNI-357
  参考文献：
  名称：

  Synthesis and biological evaluation of prodrug-type anti-HIV agents: ester conjugates of carboxylic acid-containing dipeptide HIV protease inhibitors and a reverse transcriptase inhibitor

  摘要：

  On the basis of substrate transition-state mimic concept of HIV protease, a series of small-sized dipeptide inhibitors containing hydrophilic carboxyl group were designed and synthesized. These dipeptide inhibitors showed good HIV protease inhibitory activity, but their anti-HIV activity was poor. The low antiviral activities of these inhibitors were probably due to their inadequate cell membrane permeability caused by the presence of a free carboxylic acid in the inhibitors. Based on the prodrug concept as well as the combination of two different classes of anti-HIV agents, conjugates of HIV protease inhibitors with a nucleoside reverse transcriptase inhibitor were synthesized. Some of these conjugates exhibited excellent antiviral activity compared with that of individual inhibitors. The synergistic enhancement of anti-HIV activities of these conjugates may be due to their ability to penetrate into the target cell and subsequent regeneration of two different classes of anti-HIV agents in the cytoplasm. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00261-3

文献信息

• Synthesis and biological evaluation of prodrug-type anti-HIV agents: ester conjugates of carboxylic acid-containing dipeptide HIV protease inhibitors and a reverse transcriptase inhibitor
  作者：Hikaru Matsumoto、Takashi Matsuda、Shingo Nakata、Takatoshi Mitoguchi、Tooru Kimura、Yoshio Hayashi、Yoshiaki Kiso

  DOI：10.1016/s0968-0896(00)00261-3

  日期：2001.2

  On the basis of substrate transition-state mimic concept of HIV protease, a series of small-sized dipeptide inhibitors containing hydrophilic carboxyl group were designed and synthesized. These dipeptide inhibitors showed good HIV protease inhibitory activity, but their anti-HIV activity was poor. The low antiviral activities of these inhibitors were probably due to their inadequate cell membrane permeability caused by the presence of a free carboxylic acid in the inhibitors. Based on the prodrug concept as well as the combination of two different classes of anti-HIV agents, conjugates of HIV protease inhibitors with a nucleoside reverse transcriptase inhibitor were synthesized. Some of these conjugates exhibited excellent antiviral activity compared with that of individual inhibitors. The synergistic enhancement of anti-HIV activities of these conjugates may be due to their ability to penetrate into the target cell and subsequent regeneration of two different classes of anti-HIV agents in the cytoplasm. (C) 2001 Elsevier Science Ltd. All rights reserved.