Bicyclic octahydrocyclohepta[b]pyrrol-4(1H)one derivatives as novel selective anti-hepatitis C virus agents

被引：6

作者：

Kaushik-Basu, Neerja ^{[1
]}

Ratmanova, Nina K. ^{[2
]}

Manvar, Dinesh ^{[1
]}

Belov, Dmitry S. ^{[2
,3
]}

Cevik, Ozge ^{[1
]}

Basu, Amartya ^{[1
]}

Yerukhimovich, Mark M. ^{[4
]}

Lukyanenko, Evgeny R. ^{[2
,3
]}

Andreev, Ivan A. ^{[2
,3
]}

Belov, Grigory M. ^{[2
,3
]}

Manfroni, Giuseppe ^{[5
]}

Cecchetti, Violetta ^{[5
]}

Frick, David N. ^{[4
]}

Kurkin, Alexander V. ^{[2
]}

Altieri, Andrea ^{[3
]}

Barreca, Maria Letizia ^{[5
]}

机构：

[1] Rutgers State Univ, New Jersey Med Sch, Dept Microbiol Biochem & Mol Genet, Newark, NJ 07103 USA

[2] Lomonosov Moscow State Univ, Dept Chem, GSP 2,Leninskie Gory 1-3, Moscow 119991, Russia

[3] EDASA Sci Srls, Via Stingi 37, I-66050 San Salvo, CH, Italy

[4] Univ Wisconsin, Dept Chem & Biochem, 3210 N Cramer St, Milwaukee, WI 53211 USA

[5] Univ Perugia, Dept Pharmaceut Sci, Via A Fabretti 48, I-06123 Perugia, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 122卷

基金：

俄罗斯基础研究基金会;

关键词：

Hepatitis C virus; Anti-HCV agents; Octahydrocyclohepta[b]pyrrol-4(1H)one derivatives; HCV inhibitors; Aza-Cope-Mannich reaction; REPLICATION; IDENTIFICATION; CARE; INHIBITORS; DISCOVERY; STANDARD; DRUGS;

D O I：

10.1016/j.ejmech.2016.06.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the discovery of the bicyclic octahydrocyclohepta[b]pyrrol-4(1H)-one scaffold as a new chemotype with anti-HCV activity on genotype 1b and 2a subgenomic replicons. The most potent compound 34 displayed EC50 values of 1.8 mu M and 4.5 mu M in genotype 1b and 2a, respectively, coupled with the absence of any antimetabolic effect (gt 1b SI = 112.4; gt 2a SI = 44.2) in a cell-based assay. Compound 34 did not target HCV NS5B, IRES, NS3 helicase, or selected host factors, and thus future work will involve the unique mechanism of action of these new antiviral compounds. (C) 2016 Elsevier Masson SAS. All rights

引用

页码：319 / 325

页数：7

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