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Structure‐Based Macrocyclization Yields Hepatitis C Virus NS5B Inhibitors with Improved Binding Affinities and Pharmacokinetic Properties
Author(s) -
Cummings Maxwell D.,
Lin TseI,
Hu Lili,
Tahri Abdellah,
McGowan David,
Amssoms Katie,
Last Stefaan,
Devogelaere Benoit,
Rouan MarieClaude,
Vijgen Leen,
Berke Jan Martin,
Dehertogh Pascale,
Fransen Els,
Cleiren Erna,
van der Helm Liesbet,
Fanning Gregory,
Van Emelen Kristof,
Nyanguile Origène,
Simmen Kenny,
Raboisson Pierre,
Vendeville Sandrine
Publication year - 2012
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201200110
Subject(s) - ns5b , affinities , binding affinities , chemistry , pharmacokinetics , rational design , combinatorial chemistry , stereochemistry , hepatitis c virus , small molecule , drug , chemical space , computational biology , drug discovery , hepacivirus , virology , virus , pharmacology , biochemistry , biology , nanotechnology , materials science , receptor
The concept of drug‐likeness distills the physicochemical properties of small‐molecule drugs to a set of rules. Macrocyclic drugs are known to break these rules. A structure‐based macrocyclization strategy was applied to design new hepatitis C virus NS5B inhibitors with improved pharmacokinetic properties, exemplifying a rational strategy for overcoming the confines of standard “drug‐like chemical space”.