Discovery of pentacyclic compounds as potent inhibitors of hepatitis C virus NS5B RNA polymerase

被引：38
|
作者：
Habermann, Joerg [1 ]
Capito, Elena [1 ]
Ferreira, Maria del Rosario Rico [1 ]
Koch, Uwe [1 ]
Narjes, Frank [1 ]
机构：
[1] Merck Res Labs, IRBM P Angeletti SpA, Dept Med Chem, I-00040 Pomezia, Rome, Italy
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 03期
关键词：
HCV; HCV NS5B polymerase inhibitor; Pauson-Khand reaction; 1,3]-Dipolar cycloaddition; NONSTABILIZED AZOMETHINE YLIDES; STEREOSELECTIVE-SYNTHESIS; NONNUCLEOSIDE INHIBITORS; ALLOSTERIC INHIBITORS; PROTEIN-BINDING; RECENT PROGRESS; AMINO-ACIDS; CYCLOADDITION; BENZIMIDAZOLE; ENTRY;
D O I：
10.1016/j.bmcl.2008.12.039
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
We report a new series of inhibitors for hepatitis C virus NS5B RNA polymerase containing a constrained pentacyclic scaffold. Our SAR studies led to the identification of hexahydroindolo[2,1-a] pyrrolo[3,2-d][2] benzazepines exposing basic groups. The compounds displayed a high activity in the enzyme assay and displayed good activity in the cell-based (replicon) assay in the presence of serum proteins. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：633 / 638
页数：6
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