Synthesis and biological evaluation of 1,1-difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids possessing a N9-purinylmethyl functional group at the ring.: A new class of inhibitors for purine nucleoside phosphorylases

被引：35

作者：

Yokomatsu, T

Hayakawa, Y

Suemune, K

Kihara, T

Soeda, S

Shimeno, H

Shibuya, S

机构：

[1] Tokyo Univ Pharm & Life Sci, Sch Pharm, Tokyo 1920392, Japan

[2] Fukuoka Univ, Fac Pharmaceut Sci, Jonan Ku, Fukuoka 8140180, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 19期

关键词：

enzyme inhibitors; phosphonic acids and derivatives; isosteres; mimetics; nucleotides;

D O I：

10.1016/S0960-894X(99)00495-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

1,1-Difluaro-2-(tetrahydro-3-furanyl)ethylphosphonic acids cis-3 and trans-3 possessing a N9-purinylmethyl functionality at the ring were synthesized and tested as "multi-substrate analogue" inhibitors for purine nucleoside phosphorylases. Radical cyclization of allyic alpha,alpha-difluorophosphonate (E)-7 was applied to construct the alpha,alpha-difluorophosphonate-functionalized tetrahydrofuranyl moiety. The IC50 values of cis-3 and trans-3 for human erythrocyte PNP-catalyzed phosphorylation of inosine were determined to be 88 and 320 nM, respectively. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：2833 / 2836

页数：4