The monoethyl ester of meconic acid is an active site inhibitor of HCVNS5B RNA-dependent RNA polymerase

被引：50

作者：

Pace, P ^{[1
]}

Nizi, E ^{[1
]}

Pacini, B ^{[1
]}

Pesci, S ^{[1
]}

Matassa, V ^{[1
]}

De Francesco, R ^{[1
]}

Altamura, S ^{[1
]}

Summa, V ^{[1
]}

机构：

[1] IRBM MRL Rome, Dept Med Chem & Biochem, I-00040 Pomezia, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 12期

关键词：

D O I：

10.1016/j.bmcl.2004.03.087

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Screening of the in-house sample collection for compounds with HCV NS5B RNA dependent RNA polymerase inhibition led to the identification of a new lead. Afterwards, we discovered that the screening lead, rather than containing the expected structure 1, was comprised of roughly a 1:1 mixture of meconic acid 2 and its monoethyl ester 3, with all inhibitory potency residing with 3. We propose that this compound shares critical common features for activity with alpha,gamma-diketoacids inhibitors previously discovered by our group. SAR around this molecule will be presented to provide an improved basis for structure-based ligand design. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3257 / 3261

页数：5

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