SYNTHESIS AND CONFORMATIONAL-ANALYSIS OF 2'-DEOXY-2'-(3-METHOXYBENZAMIDO)ADENOSINE, A RATIONAL-DESIGNED INHIBITOR OF TRYPANOSOMAL GLYCERALDEHYDE PHOSPHATE DEHYDROGENASE (GAPDH)

被引：24

作者：

VANCALENBERGH, S

VANDENEECKHOUT, E

HERDEWIJN, P

DEBRUYN, A

VERLINDE, C

HOL, W

CALLENS, M

VANAERSCHOT, A

ROZENSKI, J

机构：

[1] STATE UNIV GHENT,MED CHEM LAB FFW,B-9000 GHENT,BELGIUM

[2] STATE UNIV GHENT,ORGAN CHEM LAB,B-9000 GHENT,BELGIUM

[3] UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98195

[4] UNIV WASHINGTON,BIOMOLEC STRUCT PROGRAM,SEATTLE,WA 98195

[5] INT INST CELLULAR & MOLEC PATHOL,TROP DIS RES UNIT,B-1200 BRUSSELS,BELGIUM

[6] CATHOLIC UNIV LEUVEN,REGA INST,MED CHEM LAB,B-3000 LOUVAIN,BELGIUM

来源：

HELVETICA CHIMICA ACTA | 1994年 / 77卷 / 03期

关键词：

D O I：

10.1002/hlca.19940770306

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A series of 2'-benzamido-2'-deoxyadenosine analogues were synthesized in an effort to find new lead structures for the treatment of sleeping sickness. The 2'-deoxy-2'-(3-methoxybenzamido)adenosin (1h) was proved to be a selective inhibitor of the parasite glyceraldehyde 3-phosphate dehydrogenase which confirms the modeling studies. The solution-state conformation of 2'-(thiophene-2-carboxamido) analogue 1d demonstrates a 2'-endo conformation, an orientation of the thiophene ring under the ribose moiety, and the base part occupying a 'syn'/'anti' equilibrium.

引用

页码：631 / 644

页数：14

共 36 条

[31]

VANDEVEN FJM, 1988, EUR J BIOCHEM, V178, P1

[32] STRUCTURE OF GLYCOSOMAL GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM TRYPANOSOMA-BRUCEI DETERMINED FROM LAUE DATA [J].