Inhibitors of hepatitis C virus NS3•4A protease.: Part 3:: P2 proline variants

被引：49

作者：

Perni, RB ^{[1
]}

Farmer, LJ ^{[1
]}

Cottrell, KM ^{[1
]}

Court, JJ ^{[1
]}

Courtney, LF ^{[1
]}

Deininger, DD ^{[1
]}

Gates, CA ^{[1
]}

Harbeson, SL ^{[1
]}

Kim, JL ^{[1
]}

Lin, C ^{[1
]}

Lin, K ^{[1
]}

Luong, YP ^{[1
]}

Maxwell, JP ^{[1
]}

Murcko, MA ^{[1
]}

Pitlik, J ^{[1
]}

Rao, BG ^{[1
]}

Schairer, WC ^{[1
]}

Tung, RD ^{[1
]}

Van Drie, JH ^{[1
]}

Wilson, K ^{[1
]}

Thomson, JA ^{[1
]}

机构：

[1] Vertex Pharmaceut Inc, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 08期

关键词：

hepatitis C; protease inhibitors;

D O I：

10.1016/j.bmcl.2004.01.078

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We recently described the identification of an optimized alpha-ketoamide warhead for our series of HCV NS3(.)4A inhibitors. We report herein a series of HCV protease inhibitors incorporating 3-alkyl-substituted prolines in P-2. These compounds show exceptional enzymatic and cellular potency given their relatively small size. The marked enhancement of activity of these 3-substituted proline derivatives relative to previously reported 4-hydroxyproline derivatives constitutes additional evidence for the importance of the S-2 binding pocket as the defining pharmacophore for inhibition of the NS3(.)4A enzyme. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1939 / 1942

页数：4

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