Literature DB >> 18678486

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.

Pierre Raboisson1, Herman de Kock, Asa Rosenquist, Magnus Nilsson, Lourdes Salvador-Oden, Tse-I Lin, Natalie Roue, Vladimir Ivanov, Horst Wähling, Kristina Wickström, Elizabeth Hamelink, Michael Edlund, Lotta Vrang, Sandrine Vendeville, Wim Van de Vreken, David McGowan, Abdellah Tahri, Lili Hu, Carlo Boutton, Oliver Lenz, Frederic Delouvroy, Geert Pille, Dominique Surleraux, Piet Wigerinck, Bertil Samuelsson, Kenneth Simmen.   

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 [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (K(i)=0.36nM) and viral replication (replicon EC(50)=7.8nM). 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.

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Year:  2008        PMID： 18678486     DOI： 10.1016/j.bmcl.2008.07.088

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  18 in total

1.  Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding.

Authors:  Keith P Romano; Akbar Ali; William E Royer; Celia A Schiffer
Journal:  Proc Natl Acad Sci U S A       Date:  2010-11-17       Impact factor: 11.205

2.  In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435.

Authors:  Oliver Lenz; Thierry Verbinnen; Tse-I Lin; Leen Vijgen; Maxwell D Cummings; Jimmy Lindberg; Jan Martin Berke; Pascale Dehertogh; Els Fransen; Annick Scholliers; Katrien Vermeiren; Tania Ivens; Pierre Raboisson; Michael Edlund; Susan Storm; Lotta Vrang; Herman de Kock; Gregory C Fanning; Kenneth A Simmen
Journal:  Antimicrob Agents Chemother       Date:  2010-02-22       Impact factor: 5.191

Review 3.  Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C.

Authors:  Eleanor M Wilson; Elana S Rosenthal; Sarah Kattakuzhy; Lydia Tang; Shyam Kottilil
Journal:  Clin Microbiol Rev       Date:  2016-10-19       Impact factor: 26.132

4.  Highly efficient full-length hepatitis C virus genotype 1 (strain TN) infectious culture system.

Authors:  Yi-Ping Li; Santseharay Ramirez; Sanne B Jensen; Robert H Purcell; Judith M Gottwein; Jens Bukh
Journal:  Proc Natl Acad Sci U S A       Date:  2012-11-14       Impact factor: 11.205

5.  Discovery of MK-1220: A Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease with Improved Preclinical Plasma Exposure.

Authors:  Michael T Rudd; John A McCauley; John W Butcher; Joseph J Romano; Charles J McIntyre; Kevin T Nguyen; Kevin F Gilbert; Kimberly J Bush; M Katharine Holloway; John Swestock; Bang-Lin Wan; Steven S Carroll; Jillian M DiMuzio; Donald J Graham; Steven W Ludmerer; Mark W Stahlhut; Christine M Fandozzi; Nicole Trainor; David B Olsen; Joseph P Vacca; Nigel J Liverton
Journal:  ACS Med Chem Lett       Date:  2011-01-12       Impact factor: 4.345

6.  Large-scale production and structural and biophysical characterizations of the human hepatitis B virus polymerase.

Authors:  Judit Vörös; Annika Urbanek; Gilles Jean Philippe Rautureau; Maggie O'Connor; Henry C Fisher; Alison E Ashcroft; Neil Ferguson
Journal:  J Virol       Date:  2013-12-18       Impact factor: 5.103

7.  MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants.

Authors:  Vincenzo Summa; Steven W Ludmerer; John A McCauley; Christine Fandozzi; Christine Burlein; Giuliano Claudio; Paul J Coleman; Jillian M Dimuzio; Marco Ferrara; Marcello Di Filippo; Adam T Gates; Donald J Graham; Steven Harper; Daria J Hazuda; Qian Huang; Carolyn McHale; Edith Monteagudo; Vincenzo Pucci; Michael Rowley; Michael T Rudd; Aileen Soriano; Mark W Stahlhut; Joseph P Vacca; David B Olsen; Nigel J Liverton; Steven S Carroll
Journal:  Antimicrob Agents Chemother       Date:  2012-05-21       Impact factor: 5.191

8.  Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor.

Authors:  Ashok Arasappan; Frank Bennett; Stephane L Bogen; Srikanth Venkatraman; Melissa Blackman; Kevin X Chen; Siska Hendrata; Yuhua Huang; Regina M Huelgas; Latha Nair; Angela I Padilla; Weidong Pan; Russell Pike; Patrick Pinto; Sumei Ruan; Mousumi Sannigrahi; Francisco Velazquez; Bancha Vibulbhan; Wanli Wu; Weiying Yang; Anil K Saksena; Viyyoor Girijavallabhan; Neng-Yang Shih; Jianshe Kong; Tao Meng; Yan Jin; Jesse Wong; Paul McNamara; Andrew Prongay; Vincent Madison; John J Piwinski; Kuo-Chi Cheng; Richard Morrison; Bruce Malcolm; Xiao Tong; Robert Ralston; F George Njoroge
Journal:  ACS Med Chem Lett       Date:  2010-02-15       Impact factor: 4.345

9.  In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor.

Authors:  Tse-I Lin; Oliver Lenz; Gregory Fanning; Thierry Verbinnen; Frédéric Delouvroy; Annick Scholliers; Katrien Vermeiren; Asa Rosenquist; Michael Edlund; Bertil Samuelsson; Lotta Vrang; Herman de Kock; Piet Wigerinck; Pierre Raboisson; Kenneth Simmen
Journal:  Antimicrob Agents Chemother       Date:  2009-01-26       Impact factor: 5.191

Review 10.  Tetrazoles via Multicomponent Reactions.

Authors:  Constantinos G Neochoritis; Ting Zhao; Alexander Dömling
Journal:  Chem Rev       Date:  2019-02-01       Impact factor: 60.622
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