Structure‐Based Macrocyclization Yields Hepatitis C Virus NS5B Inhibitors with Improved Binding Affinities and Pharmacokinetic Properties
2012; Wiley; Volume: 51; Issue: 19 Linguagem: Inglês
10.1002/anie.201200110
ISSN1521-3773
AutoresMaxwell D. Cummings, Tse‐I Lin, Lili Hu, Abdellah Tahri, David C. McGowan, Katie Amssoms, Stefaan Last, Benoit Devogelaere, M.C. Rouan, Leen Vijgen, Jan Martin Berke, Pascale Dehertogh, Els Fransen, Erna Cleiren, Liesbet van der Helm, Gregory Fanning, Kristof Van Emelen, Origène Nyanguile, Kenny Simmen, Pierre Raboisson, Sandrine Vendeville,
Tópico(s)Synthetic Organic Chemistry Methods
ResumoAngewandte Chemie International EditionVolume 51, Issue 19 p. 4637-4640 Communication Structure-Based Macrocyclization Yields Hepatitis C Virus NS5B Inhibitors with Improved Binding Affinities and Pharmacokinetic Properties Dr. Maxwell D. Cummings, Corresponding Author Dr. Maxwell D. Cummings svendev1@its.jnj.com mcummin1@its.jnj.com Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium) Janssen Research & Development, Welsh & McKean Roads, Spring House, PA 19477 (USA)Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Tse-I Lin, Dr. Tse-I Lin Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorLili Hu, Lili Hu Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Abdellah Tahri, Dr. Abdellah Tahri Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDavid McGowan, David McGowan Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Katie Amssoms, Dr. Katie Amssoms Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorStefaan Last, Stefaan Last Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Benoit Devogelaere, Dr. Benoit Devogelaere Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium) Biocartis NV, Mechelen (Belgium)Search for more papers by this authorMarie-Claude Rouan, Marie-Claude Rouan Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Leen Vijgen, Dr. Leen Vijgen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Jan Martin Berke, Dr. Jan Martin Berke Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorPascale Dehertogh, Pascale Dehertogh Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorEls Fransen, Els Fransen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorErna Cleiren, Erna Cleiren Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorLiesbet van der Helm, Liesbet van der Helm Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Gregory Fanning, Dr. Gregory Fanning Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Kristof Van Emelen, Dr. Kristof Van Emelen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorProf. Dr. Origène Nyanguile, Prof. Dr. Origène Nyanguile Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium) University of Applied Sciences, Institute of Life Technologies, Rte du Rawyl 47, 1950 Sion 2 (Switzerland)Search for more papers by this authorDr. Kenny Simmen, Dr. Kenny Simmen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Pierre Raboisson, Dr. Pierre Raboisson Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Sandrine Vendeville, Corresponding Author Dr. Sandrine Vendeville Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this author Dr. Maxwell D. Cummings, Corresponding Author Dr. Maxwell D. Cummings svendev1@its.jnj.com mcummin1@its.jnj.com Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium) Janssen Research & Development, Welsh & McKean Roads, Spring House, PA 19477 (USA)Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Tse-I Lin, Dr. Tse-I Lin Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorLili Hu, Lili Hu Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Abdellah Tahri, Dr. Abdellah Tahri Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDavid McGowan, David McGowan Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Katie Amssoms, Dr. Katie Amssoms Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorStefaan Last, Stefaan Last Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Benoit Devogelaere, Dr. Benoit Devogelaere Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium) Biocartis NV, Mechelen (Belgium)Search for more papers by this authorMarie-Claude Rouan, Marie-Claude Rouan Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Leen Vijgen, Dr. Leen Vijgen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Jan Martin Berke, Dr. Jan Martin Berke Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorPascale Dehertogh, Pascale Dehertogh Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorEls Fransen, Els Fransen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorErna Cleiren, Erna Cleiren Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorLiesbet van der Helm, Liesbet van der Helm Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Gregory Fanning, Dr. Gregory Fanning Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Kristof Van Emelen, Dr. Kristof Van Emelen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorProf. Dr. Origène Nyanguile, Prof. Dr. Origène Nyanguile Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium) University of Applied Sciences, Institute of Life Technologies, Rte du Rawyl 47, 1950 Sion 2 (Switzerland)Search for more papers by this authorDr. Kenny Simmen, Dr. Kenny Simmen Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Pierre Raboisson, Dr. Pierre Raboisson Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this authorDr. Sandrine Vendeville, Corresponding Author Dr. Sandrine Vendeville Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Janssen Infectious Diseases BVBA (formerly Tibotec BVBA), Turnhoutseweg 30, 2340 Beerse (Belgium)Search for more papers by this author First published: 30 March 2012 https://doi.org/10.1002/anie.201200110Citations: 30Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat 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". Citing Literature Supporting Information Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Filename Description anie_201200110_sm_miscellaneous_information.pdf779.4 KB miscellaneous_information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume51, Issue19May 7, 2012Pages 4637-4640 RelatedInformation
Referência(s)