MISC

査読有り
2001年

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

Bioorganic and Medicinal Chemistry
  • Hikaru Matsumoto
  • ,
  • Takashi Matsuda
  • ,
  • Shingo Nakata
  • ,
  • Takatoshi Mitoguchi
  • ,
  • Tooru Kimura
  • ,
  • Yoshio Hayashi
  • ,
  • Yoshiaki Kiso

9
2
開始ページ
417
終了ページ
430
記述言語
英語
掲載種別
DOI
10.1016/S0968-0896(00)00261-3

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. © 2001 Elsevier Science Ltd.

リンク情報
DOI
https://doi.org/10.1016/S0968-0896(00)00261-3
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/11249134

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