Literature DB >> 18338894

Molecular modeling based approach to potent P2-P4 macrocyclic inhibitors of hepatitis C NS3/4A protease.

Nigel J Liverton1, M Katharine Holloway, John A McCauley, Michael T Rudd, John W Butcher, Steven S Carroll, Jillian DiMuzio, Christine Fandozzi, Kevin F Gilbert, Shi-Shan Mao, Charles J McIntyre, Kevin T Nguyen, Joseph J Romano, Mark Stahlhut, Bang-Lin Wan, David B Olsen, Joseph P Vacca.   

Abstract

Molecular modeling of inhibitor bound full length HCV NS3/4A protease structures proved to be a valuable tool in the design of a new series of potent NS3 protease inhibitors. Optimization of initial compounds provided 25a. The in vitro activity and selectivity as well as the rat pharmacokinetic profile of 25a compare favorably with the data for other NS3/4A protease inhibitors currently in clinical development for the treatment of HCV.

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Year:  2008        PMID： 18338894     DOI： 10.1021/ja711120r

Source DB:  PubMed          Journal:  J Am Chem Soc        ISSN： 0002-7863            Impact factor:   15.419


  20 in total

1.  A macrocyclic HCV NS3/4A protease inhibitor interacts with protease and helicase residues in the complex with its full-length target.

Authors:  Nikolaus Schiering; Allan D'Arcy; Frederic Villard; Oliver Simic; Marion Kamke; Gaby Monnet; Ulrich Hassiepen; Dmitri I Svergun; Ruth Pulfer; Jörg Eder; Prakash Raman; Ursula Bodendorf
Journal:  Proc Natl Acad Sci U S A       Date:  2011-12-12       Impact factor: 11.205

2.  Modeling & Informatics at Vertex Pharmaceuticals Incorporated: our philosophy for sustained impact.

Authors:  Georgia McGaughey; W Patrick Walters
Journal:  J Comput Aided Mol Des       Date:  2016-11-29       Impact factor: 3.686

3.  Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor.

Authors:  Steven Harper; John A McCauley; Michael T Rudd; Marco Ferrara; Marcello DiFilippo; Benedetta Crescenzi; Uwe Koch; Alessia Petrocchi; M Katharine Holloway; John W Butcher; Joseph J Romano; Kimberly J Bush; Kevin F Gilbert; Charles J McIntyre; Kevin T Nguyen; Emanuela Nizi; Steven S Carroll; Steven W Ludmerer; Christine Burlein; Jillian M DiMuzio; Donald J Graham; Carolyn M McHale; Mark W Stahlhut; David B Olsen; Edith Monteagudo; Simona Cianetti; Claudio Giuliano; Vincenzo Pucci; Nicole Trainor; Christine M Fandozzi; Michael Rowley; Paul J Coleman; Joseph P Vacca; Vincenzo Summa; Nigel J Liverton
Journal:  ACS Med Chem Lett       Date:  2012-03-02       Impact factor: 4.345

4.  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

5.  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

6.  Simultaneously Targeting the NS3 Protease and Helicase Activities for More Effective Hepatitis C Virus Therapy.

Authors:  Jean Ndjomou; M Josie Corby; Noreena L Sweeney; Alicia M Hanson; Cihan Aydin; Akbar Ali; Celia A Schiffer; Kelin Li; Kevin J Frankowski; Frank J Schoenen; David N Frick
Journal:  ACS Chem Biol       Date:  2015-05-22       Impact factor: 5.100

7.  Pharmacodynamic analysis of a serine protease inhibitor, MK-4519, against hepatitis C virus using a novel in vitro pharmacodynamic system.

Authors:  Ashley N Brown; James J McSharry; Jonathan R Adams; Robert Kulawy; Richard J O Barnard; W Newhard; A Corbin; Daria J Hazuda; Arnold Louie; George L Drusano
Journal:  Antimicrob Agents Chemother       Date:  2011-12-12       Impact factor: 5.191

8.  Structural and Thermodynamic Effects of Macrocyclization in HCV NS3/4A Inhibitor MK-5172.

Authors:  Djadé I Soumana; Nese Kurt Yilmaz; Kristina L Prachanronarong; Cihan Aydin; Akbar Ali; Celia A Schiffer
Journal:  ACS Chem Biol       Date:  2016-01-06       Impact factor: 5.100

9.  Evaluating the role of macrocycles in the susceptibility of hepatitis C virus NS3/4A protease inhibitors to drug resistance.

Authors:  Akbar Ali; Cihan Aydin; Reinhold Gildemeister; Keith P Romano; Hong Cao; Ayşegül Ozen; Djade Soumana; Alicia Newton; Christos J Petropoulos; Wei Huang; Celia A Schiffer
Journal:  ACS Chem Biol       Date:  2013-05-01       Impact factor: 5.100

10.  MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease.

Authors:  Nigel J Liverton; Steven S Carroll; Jillian Dimuzio; Christine Fandozzi; Donald J Graham; Daria Hazuda; M Katherine Holloway; Steven W Ludmerer; John A McCauley; Charles J McIntyre; David B Olsen; Michael T Rudd; Mark Stahlhut; Joseph P Vacca
Journal:  Antimicrob Agents Chemother       Date:  2009-10-19       Impact factor: 5.191
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