Effect of the acyl groups on O→N acyl migration in the water-soluble Prodrugs of HIV-1 protease inhibitor

被引：25

作者：

Hamada, Y ^{[1
]}

Matsumoto, H ^{[1
]}

Kimura, T ^{[1
]}

Hayashi, Y ^{[1
]}

Kiso, Y ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(03)00576-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To improve the low water-solubility of HIV-1 protease inhibitors KNI-272, -279 and -727, we previously reported the water-soluble prodrugs of these inhibitors based on O-->N intramolecular acyl migration reaction. These prodrugs were rapidly converted to the corresponding parent drugs under physiological conditions. To understand the steric and electrostatic effects of O-acyl moiety on the migration rate, we examined several types of prodrug. A remarkably slow migration was observed in the benzoyl-type prodrugs, and Hammett plot of migration rate constants of p-substituted benzoyl-type prodrugs gave a linear free energy relationship. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：2727 / 2730

页数：4

共 26 条

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