Structure-based macrocyclization yields hepatitis C virus NS5B inhibitors with improved binding affinities and pharmacokinetic properties
2012
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Abstract
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”.
Details
Title
Structure-based macrocyclization yields hepatitis C virus NS5B inhibitors with improved binding affinities and pharmacokinetic properties
Author(s)
Cummings, M. D. (Janssen Infectious Diseases BVBA, Beerse, Belgium ; Welsh & McKean Roads, Spring House, PA, USA)
Lin, T. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Hu, L. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Tahri, A. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
McGowan, D. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Amssoms, K. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Last, S. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Devogelaere, B. (Janssen Infectious Diseases BVBA, Beerse, Belgium ; Biocartis NV, Mechelen, Belgium)
Rouan, M.-C. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Vijgen, L. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Berke, J. M. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Dehertogh, P. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Fransen, E. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Cleiren, E. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
van der Helm, L. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Fanning, G. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Van Emelen, K. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Nyanguile, Origène (Janssen Infectious Diseases BVBA, Beerse, Belgium ; School of Engineering, HES-SO Valais-Wallis, HEI, HES-SO University of Applied Sciences Western Switzerland)
Simmen, K. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Raboisson, P. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Vendeville, S. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Lin, T. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Hu, L. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Tahri, A. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
McGowan, D. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Amssoms, K. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Last, S. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Devogelaere, B. (Janssen Infectious Diseases BVBA, Beerse, Belgium ; Biocartis NV, Mechelen, Belgium)
Rouan, M.-C. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Vijgen, L. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Berke, J. M. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Dehertogh, P. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Fransen, E. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Cleiren, E. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
van der Helm, L. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Fanning, G. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Van Emelen, K. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Nyanguile, Origène (Janssen Infectious Diseases BVBA, Beerse, Belgium ; School of Engineering, HES-SO Valais-Wallis, HEI, HES-SO University of Applied Sciences Western Switzerland)
Simmen, K. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Raboisson, P. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Vendeville, S. (Janssen Infectious Diseases BVBA, Beerse, Belgium)
Date
2012-03
Published in
Angewandte Chemie International Edition
Volume
2012, vol. 51, no. 19, pp. 4637-4640
Pagination
4 p.
ISSN
1433-7851
Keywords
hepatitis C virus ; inhibitors ; macrocycles ; polmyerases ; pharmacokinetics
Article Type
scientifique
Faculty
Ingénierie et Architecture
School
HEI-VS
Institute
Institut Technologies du vivant
Record Appears in
Scientific Articles
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