SYNTHESIS OF 9-(1-DEOXY-1-PHOSPHONO-BETA-D-PSICOFURANOSYL)-1,9-DIHYDRO-6H-PURIN-6-ONE AS A POTENTIAL TRANSITION-STATE ANALOG INHIBITOR OF PURINE NUCLEOSIDE PHOSPHORYLASE

被引：32

作者：

ELLIOTT, RD

NIWAS, S

RIORDAN, JM

MONTGOMERY, JA

SECRIST, JA

机构：

[1] Kettering-Meyer Laboratories, Southern research Institute, Birmingham AL 35255-5305

来源：

NUCLEOSIDES & NUCLEOTIDES | 1992年 / 11卷 / 01期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

D O I：

10.1080/07328319208021155

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：

A fifteen-step synthesis of the proposed purine nucleoside phosphorylase (PNP) transition state analog inhibitor 9-(1-deoxy-1-phosphono-beta-D-psicofuranosyl)-1,9-dihydro-6H-purine-6-one (2) is described starting with 1,2:4,5-disopropylidene-beta-D-psicopyranose (12). Catalytic hydrogenation of 9-[3-O-benzyl-1-(dibenzyloxy-phosphinyl)-1-deoxy-beta-D-psicofuranosyl]-6-benzyloxypurine (27b) under basic conditions gave the unstable 2 which was found to have a half-life of 39 min at pH 7 and 81 min at pH 8. The low PNP inhibitory activity found for 2 (IC50 = 25-mu-M at 50 mM phosphate concentration) may be due entirely to the presence of the decomposition product hypoxanthine which is itself an inhibitor (IC50 = 8.6-mu-M).

引用

页码：97 / 119

页数：23

共 30 条

[1]

BABU YS, UNPUB

[2] PHOSPHONAMIDATES AS TRANSITION-STATE ANALOG INHIBITORS OF THERMOLYSIN [J].