862175-03-9Relevant academic research and scientific papers
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
Raboisson, Pierre,de Kock, Herman,Rosenquist, Asa,Nilsson, Magnus,Salvador-Oden, Lourdes,Lin, Tse-I,Roue, Natalie,Ivanov, Vladimir,Waehling, Horst,Wickstroem, Kristina,Hamelink, Elizabeth,Edlund, Michael,Vrang, Lotta,Vendeville, Sandrine,Van de Vreken, Wim,McGowan, David,Tahri, Abdellah,Hu, Lili,Boutton, Carlo,Lenz, Oliver,Delouvroy, Frederic,Pille, Geert,Surleraux, Dominique,Wigerinck, Piet,Samuelsson, Bertil,Simmen, Kenneth
experimental part, p. 4853 - 4858 (2009/05/11)
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)sulfonamid e (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.
HCV NS-3 SERINE PROTEASE INHIBITORS
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Page/Page column 141, (2008/06/13)
Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.
