异核苷的合成及其抗HIV活性

Synthesis and anti-HIV activity of isonucleosides.

作者信息

Huryn D M, Sluboski B C, Tam S Y, Weigele M, Sim I, Anderson B D, Mitsuya H, Broder S

机构信息

Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.

出版信息

J Med Chem. 1992 Jun 26;35(13):2347-54. doi: 10.1021/jm00091a001.

DOI:10.1021/jm00091a001

PMID:1619614

Abstract

A series of isomeric 2',3'-dideoxynucleosides which contains a modified carbohydrate moiety has been prepared. This class of compounds was designed to mimic the activity of known anti-HIV dideoxynucleosides, while imparting enhanced chemical and enzymatic stability. Isonucleosides containing the standard heterocyclic bases (A, C, G, T) were synthesized via nucleophilic addition of the base to an isomeric sugar unit. Modified derivatives were generated by manipulation of the intact isonucleoside. Two of the compound prepared, iso-ddA (1) and iso-ddG (6), exhibit significant and selective anti-HIV activity, as well as beneficial hydrolytic stability.

摘要

已制备出一系列含有修饰碳水化合物部分的2',3'-二脱氧核苷异构体。设计这类化合物是为了模拟已知抗HIV二脱氧核苷的活性，同时提高其化学和酶稳定性。通过将碱基亲核加成到异构糖单元上，合成了含有标准杂环碱基（A、C、G、T）的异核苷。通过对完整异核苷进行操作生成修饰衍生物。所制备的两种化合物，异-双脱氧腺苷（1）和异-双脱氧鸟苷（6），表现出显著的选择性抗HIV活性以及良好的水解稳定性。