Synthesis and evaluation of non-dimeric HCV NS5A inhibitors

Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a s...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2013-04, Vol.23 (7), p.2031-2034
Hauptverfasser:	Amblard, Franck, Zhang, Hongwang, Zhou, Longhu, Shi, Junxing, Bobeck, Drew R., Nettles, James H., Chavre, Satish, McBrayer, Tamara R., Tharnish, Philip, Whitaker, Tony, Coats, Steven J., Schinazi, Raymond F.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antiviral agent Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Carbamates Cell Line Chlorocebus aethiops Dose-Response Relationship, Drug HCV Hepacivirus - drug effects Humans Imidazoles - chemical synthesis Imidazoles - chemistry Imidazoles - pharmacology Microbial Sensitivity Tests Molecular Structure NS5A Pyrrolidines Structure-Activity Relationship Valine - analogs & derivatives Vero Cells Viral Nonstructural Proteins - antagonists & inhibitors Virus Replication - drug effects
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Zusammenfassung:	Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a showed picomolar range activity along with an excellent selectivity index (SI > 90,000).
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2013.02.023