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

被引：29

作者：

Matsumoto, H ^{[1
]}

Sohma, Y ^{[1
]}

Kimura, T ^{[1
]}

Hayashi, Y ^{[1
]}

Kiso, Y ^{[1
]}

机构：

[1] Kyoto Pharmaceut Univ, Ctr Frontier Res Med Sci, Dept Med Chem, Yamashina Ku, Kyoto 6078412, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(01)00007-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (>10(4) 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. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：605 / 609

页数：5

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