Synthesis and evaluation of non-dimeric HCV NS5A inhibitors

  • Bioorg Med Chem Lett. 2013 Apr 1;23(7):2031-4. doi: 10.1016/j.bmcl.2013.02.023.
Franck Amblard  1 ,  Hongwang Zhang ,  Longhu Zhou ,  Junxing Shi ,  Drew R Bobeck ,  James H Nettles ,  Satish Chavre ,  Tamara R McBrayer ,  Philip Tharnish ,  Tony Whitaker ,  Steven J Coats ,  Raymond F Schinazi
Affiliations
  • 1. Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
PMID: 23466233 DOI: 10.1016/j.bmcl.2013.02.023
Abstract

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).