Toward the discovery of dual HCMV-VZV inhibitors: Synthesis, structure activity relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N-(4-phenoxyphenyl)acetamides

被引：11

作者：

Babkov, Denis A. ^{[1
]}

Khandazhinskaya, Anastasia L. ^{[2
]}

Chizhov, Alexander O. ^{[3
]}

Andrei, Graciela ^{[4
]}

Snoeck, Robert ^{[4
]}

Seley-Radtke, Katherine L. ^{[5
]}

Novikov, Mikhail S. ^{[1
]}

机构：

[1] Volgograd State Med Univ, Dept Pharmaceut & Toxicol Chem, Volgograd 400131, Russia

[2] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia

[3] Russian Acad Sci, Zelinsky Inst Organ Chem, Moscow 119991, Russia

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

[5] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 21期

基金：

俄罗斯基础研究基金会;

关键词：

Human cytomegalovirus; Varicella zoster virus; Antiviral; Non-nucleoside inhibitor; Uracil; HUMAN CYTOMEGALOVIRUS; NUCLEOSIDE ANALOGS; DERIVATIVES; POLYMERASE; AGENTS; PREVENTION; MANAGEMENT; DESIGN; ACID; CMV;

D O I：

10.1016/j.bmc.2015.09.033

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：

The need for novel therapeutic options to fight herpesvirus infections still persists. Herein we report the design, synthesis and antiviral evaluation of a new family of non-nucleoside antivirals, derived from 1-[omega-(4-bromophenoxy)alkyl]uracil derivatives - previously reported inhibitors of human cytomegalovirus (HCMV). Introduction of the N-(4-phenoxyphenyl)acetamide side chain at N-3 increased their potency and widened activity spectrum. The most active compounds in the series exhibit submicromolar activity against different viral strains of HCMV and varicella zoster virus (VZV) replication in HEL cell cultures. Inactivity against other DNA and RNA viruses, including herpes simplex virus 1/2, points to a novel mechanism of antiviral action. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：7035 / 7044

页数：10

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