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Structure-based macrocyclization yields hepatitis C virus NS5B inhibitors with improved binding affinities and pharmacokinetic properties

Cummings, M. D.; Lin, T.; Hu, L.; Tahri, A.; McGowan, D.; Amssoms, K.; Last, S.; Devogelaere, B.; Rouan, M.-C.; Vijgen, L.; Berke, J. M.; Dehertogh, P.; Fransen, E.; Cleiren, E.; van der Helm, L.; Fanning, G.; Van Emelen, K.; Nyanguile, Origène; Simmen, K.; Raboisson, P.; Vendeville, S.
2012
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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”.

Titre
Structure-based macrocyclization yields hepatitis C virus NS5B inhibitors with improved binding affinities and pharmacokinetic properties
Auteur(s)/ trice(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)
Date
2012-03
Publié dans
Angewandte Chemie International Edition
Volume
2012, vol. 51, no. 19, pp. 4637-4640
Pagination & équivalents
4 p.
DOI
https://doi.org/10.1002/anie.201200110
Mots-clés (libres)
hepatitis C virus ; inhibitors ; macrocycles ; polmyerases ; pharmacokinetics
Type d'article
scientifique
Domaine
Ingénierie et Architecture
Ecole
HEI-VS
Institut
Institut Technologies du vivant
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Articles scientifiques
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