Title of article
Structure–activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350
Author/Authors
Pierre Raboisson، نويسنده , , Herman de Kock، نويسنده , , Asa Rosenquist، نويسنده , , Magnus Nilsson، نويسنده , , Lourdes Salvador-Oden، نويسنده , , Tse-I Lin، نويسنده , , Natalie Roue، نويسنده , , Vladimir Ivanov، نويسنده , , Horst W?hling، نويسنده , , Kristina Wickstr?m، نويسنده , , Elizabeth Hamelink، نويسنده , , Michael Edlund، نويسنده , , Lotta Vrang، نويسنده , , Sandrine Vendeville، نويسنده , , Wim Van de Vreken، نويسنده , , David McGowan، نويسنده , , Abdellah Tahri، نويسنده , , Lili Hu، نويسنده , , Carlo Boutton، نويسنده , , Oliver Lenz، نويسنده , , et al.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2008
Pages
6
From page
4853
To page
4858
Abstract
SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (Ki = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics.
Keywords
Hepatitis C , protease , NS3 , Macrocycle
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2008
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
799904
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