6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines:: A new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity

被引:26
作者
Balzarini, J [1 ]
Pannecouque, C
Naesens, L
Andrei, G
Snoeck, R
De Clercq, E
Hocková, D
Holy, A
机构
[1] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium
[2] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Prague 6, Czech Republic
关键词
acyclic nucleoside phosphonates; HIV; AIDS; herpesviruses; poxviruses; hepadnaviruses;
D O I
10.1081/NCN-200027573
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
Acyclic nucleoside phosphonate derivatives containing a pyrimidine base preferably bearing amino groups at C-2 and C-4 (DAPym), and linked at the C-6 position to (S)[3-hydroxy-2-(phosphonomethoxy)propoxy] (HPMPO), 2-(phosphonomethoxy) ethoxy (PMEO) or (R)-[2-(phosphonomethoxy)propoxy] (PMPO), display an antiviral sensitivity spectrum that closely mimic that of the parental (S)-HPMP-, PME- and (R)PMP-purine derivatives. Several PMEO-DAPym derivatives proved as potent as PMEA (adefovir) and (R)-PMPA (tenofovir) in inhibiting Moloney murine sarcoma virus (MSV)-induced tumor formation in newborn NMRI mice. The HPMPO-, PMEO- and PMPO-DAPym derivatives represent a novel well-defined subclass among the acyclic nucleoside phosphonates endowed with potent and selective antiviral activity.
引用
收藏
页码:1321 / 1327
页数:7
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