Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase

被引：78

作者：

Evans, GB

Furneaux, RH

Lewandowicz, A

Schramm, VL

Tyler, PC

机构：

[1] Ind Res Ltd, Carbohydrate Chem, Lower Hutt, New Zealand

[2] Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 15期

关键词：

D O I：

10.1021/jm030145r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The aza-C-nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2'-, 3'-, or 5'-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.

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页码：3412 / 3423

页数：12

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