Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE acyclic moiety

被引：11

作者：

Tichy, Tomas ^{[1
]}

Andrei, Graciela ^{[2
]}

Snoeck, Robert ^{[2
]}

Balzarini, Jan ^{[2
]}

Dracinsky, Martin ^{[1
]}

Krecmerova, Marcela ^{[1
]}

机构：

[1] Acad Sci Czech Republic, Inst Organ Chem & Biochem, CR-16610 Prague, Czech Republic

[2] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷

关键词：

Antivirals; Prodrugs; Acyclic nucleoside phosphonate; Phosphonate ester; In vitro evaluation; IN-VITRO; ESTERS; PHOSPHORIBOSYLTRANSFERASE; CYTOMEGALOVIRUS; DERIVATIVES; CIDOFOVIR; DIESTERS;

D O I：

10.1016/j.ejmech.2012.07.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)-HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The activity of the prodrugs was evaluated in vitro against different virus families. Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive, monoesters of PEEG, and mono- and diesters of (S)-HPMPG showed pronounced antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)-HPMPG emerged as the most potent and selective derivatives against these DNA viruses. None of the compounds were inhibitory against RNA viruses and retroviruses. Crown Copyright (C) 2012 Published by Elsevier Masson SAS. All rights reserved.

引用

页码：307 / 314

页数：8

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