Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication

  • ACS Med Chem Lett. 2015 Nov 23;7(1):17-22. doi: 10.1021/acsmedchemlett.5b00402.
Longhu Zhou  1 ,  Hongwang Zhang  1 ,  Sijia Tao  1 ,  Maryam Ehteshami  1 ,  Jong Hyun Cho  1 ,  Tamara R McBrayer  2 ,  Philip Tharnish  2 ,  Tony Whitaker  2 ,  Franck Amblard  1 ,  Steven J Coats  2 ,  Raymond F Schinazi  1
Affiliations
  • 1. Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center , Atlanta, Georgia 30322, United States.
  • 2. CoCrystal Pharma, Inc. , Tucker, Georgia 30084, United States.
PMID: 26819659 DOI: 10.1021/acsmedchemlett.5b00402
Abstract

A variety of 2,6-modified purine 2'-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported.

Keywords
HCV; antiviral; nucleoside; phosphoramidate prodrug; purine.