8-aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases

被引：59

作者：

Evans, GB

Furneaux, RH

Gainsford, GJ

Hanson, JC

Kicska, GA

Sauve, AA

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

[3] Brookhaven Natl Lab, Upton, NY 11973 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 01期

关键词：

D O I：

10.1021/jm0203332

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 8-aza-immucillins (8-aza-9-deazapurines linked from C9 to C1 of 1,4-dideoxy-1,4-iminoribitol) have been designed as transition-state analogues of the reactions catalyzed by purine nucleoside phosphorylase and nucleoside hydrolases. Syntheses of the 8-aza-immucillin analogues of inosine and adenosine are described. They are powerful inhibitors of the target enzymes with equilibrium dissociation constants as low as 42 pM.

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页码：155 / 160

页数：6

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