PHOSPHORAMIDATE DERIVATIVES OF AZT AS INHIBITORS OF HIV - STUDIES ON THE CARBOXYL TERMINUS

被引：21

作者：

MCGUIGAN, C ^{[1
]}

PATHIRANA, RN ^{[1
]}

CHOI, SSM ^{[1
]}

KINCHINGTON, D ^{[1
]}

OCONNOR, TJ ^{[1
]}

机构：

[1] ST BARTHOLOMEWS HOSP & MED COLL, LONDON EC1A 7BE, ENGLAND

来源：

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY | 1993年 / 4卷 / 02期

关键词：

D O I：

10.1177/095632029300400204

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Novel phosphoramidate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials carry carboxy-protected, amino acids, and are designed to act as membrane-soluble prodrugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity. In particular, variation in the carboxy terminus region is studied. For alkyl phosphates small changes in the structure of the amino ester lead to marked changes in biological activity. However, for analogous aryl phosphates there is little dependence on the structure of the ester. This suggests a different mechanism of action for these two categories of phosphate prodrug.

引用

页码：97 / 101

页数：5

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