Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues.: Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase

被引：43
作者：
Yokomatsu, T
Abe, H
Sato, M
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 | 1998年 / 6卷 / 12期
关键词：
enzyme inhibitors; mimetics; nucleotides; phosphonic acids and derivatives;
D O I：
10.1016/S0968-0896(98)80023-0
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 series of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids, (E)-2a,b and (Z)-2a,b, as well as the related methano analogues (+/-)-3a,b and (+/-)-4a,b were prepared for evaluation of their PNP inhibitory activities. The cyclopopane ring and the hypoxanthine residue were found to increase the profile of inhibitory activity. The IC50 and K-i values of difluoro({1R*,2S*)-2-[2-(6-oxo-6,9-dihydro-1H-9-purinyl)ethyl]cyclopropyl)methylphosphonic acid (+/-)3b toward PNP purified from Cellulomonas sp. were determined to be 70 nM and 8.8 nM, respectively. (C) 1998 Elsevier Science Ltd. All rights reserved.
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收藏
页码：2495 / 2505
页数：11
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