113206-03-4Relevant articles and documents
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Clemo,Daglish
, p. 1481,1483 (1950)
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TRPV4 ANTAGONISTS
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Page/Page column 46, (2011/10/13)
The present invention relates to quinoline analogs, pharmaceutical compositions containing them and their use as TRPV4 antagonists.
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
scheme or table, 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.