2. Academic Validation
  3. Design, synthesis and evaluation of novel anti-HCV molecules that deliver intracellularly three highly potent NS5A inhibitors

Design, synthesis and evaluation of novel anti-HCV molecules that deliver intracellularly three highly potent NS5A inhibitors

  • Bioorg Med Chem Lett. 2015 Sep 1;25(17):3711-5. doi: 10.1016/j.bmcl.2015.06.031.
Sebastien Boucle 1,  Sijia Tao 1,  Franck Amblard 1,  Richard A Stanton 1,  James H Nettles 1,  Chengwei Li 1,  Tamara R McBrayer 2,  Tony Whitaker 2,  Steven J Coats 2,  Raymond F Schinazi 3
Affiliations

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.
  • 2 CoCrystal Pharma, Inc., Tucker, GA 30084, USA.
  • 3 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. Electronic address: [email protected].
PMID: 26099532 DOI: 10.1016/j.bmcl.2015.06.031
Abstract

The design and synthesis of new non-symmetrical NS5A inhibitors with sulfur containing Amino acids is reported along with their ability to block HCV replication in an HCV 1b replicon system. These compounds display EC50 values in the picomolar range with a large therapeutic index (>10(6)). Moreover, cellular pharmacology studies show that our preferred compounds intracellularly deliver three potent NS5A inhibitors.

Keywords

Antiviral; HCV; NS5A.

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