HCV NS5A replication complex inhibitors. Part 5: Discovery of potent and pan-genotypic glycinamide cap derivatives

被引：15

作者：

Belema, Makonen ^{[1
]}

Nguyen, Van N. ^{[1
]}

St. Laurent, Denis R. ^{[1
]}

Lopez, Omar D. ^{[1
]}

Qiu, Yuping ^{[1
]}

Good, Andrew C. ^{[3
]}

Nower, Peter T. ^{[2
]}

Valera, Lourdes ^{[2
]}

O'Boyle, Donald R., II ^{[2
]}

Sun, Jin-Hua ^{[2
]}

Liu, Mengping ^{[2
]}

Fridell, Robert A. ^{[2
]}

Lemm, Julie A. ^{[2
]}

Gao, Min ^{[2
]}

Knipe, Jay O. ^{[4
]}

Meanwell, Nicholas A. ^{[1
]}

Snyder, Lawrence B. ^{[1
]}

机构：

[1] Bristol Myers Squibb Res & Dev, Dept Med Chem, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Res & Dev, Dept Virol, Wallingford, CT 06492 USA

[3] Bristol Myers Squibb Res & Dev, Dept Comp Aided Drug Design, Wallingford, CT 06492 USA

[4] Bristol Myers Squibb Res & Dev, Dept Metab & Pharmacokinet, Wallingford, CT 06492 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 15期

关键词：

Daclatasvir; HCV; NS5A; Mandelamide X-ray; Pan-genotype HCV replicon inhibition; Phenylglycine; HEPATITIS-C VIRUS; PLUS RIBAVIRIN; THERAPY; DACLATASVIR; ASUNAPREVIR; INFECTION;

D O I：

10.1016/j.bmcl.2013.05.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The isoquinolinamide series of HCV NS5A inhibitors exemplified by compounds 2b and 2c provided the first dual genotype-1a/1b (GT-1a/1b) inhibitor class that demonstrated a significant improvement in potency toward GT-1a replicons compared to that of the initial program lead, stilbene 2a. Structure-activity relationship (SAR) studies that uncovered an alternate phenylglycine-based cap series that exhibit further improvements in virology profile, along with some insights into the pharmacophoric elements associated with the GT-1a potency, are described. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4428 / 4435

页数：8

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