MISC

査読有り
2001年2月26日

Controlled drug release: New water-soluble prodrugs of an HIV protease inhibitor

Bioorganic and Medicinal Chemistry Letters
  • Hikaru Matsumoto
  • ,
  • Youhei Sohma
  • ,
  • Tooru Kimura
  • ,
  • Yoshio Hayashi
  • ,
  • Yoshiaki Kiso

11
4
開始ページ
605
終了ページ
609
記述言語
英語
掲載種別
DOI
10.1016/S0960-894X(01)00007-5

We designed and synthesized a series of highly water-soluble prodrugs of an HIV protease inhibitor, KNI-727 (1), containing tandem-linked two auxiliary units, a solubilizing moiety and a self-cleavable spacer. Prodrugs with an ionized amino group at the solubilizing moiety exhibited a remarkable increase of water-solubility (&gt
104 fold) compared to the parent drug 1. These prodrugs released 1 not enzymatically, but chemically via an intramolecular cyclization-elimination reaction through an imide formation in physiological conditions. Diversified rates of parent drug release were observed when the chemical structure of both the solubilizing and the spacer moieties were modified. This new approach for water-soluble prodrugs will enable to control chemically the release of parent drug as well as to maintain high water-solubility. © 2001 Elsevier Science Ltd.

リンク情報
DOI
https://doi.org/10.1016/S0960-894X(01)00007-5
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/11229781

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