Potent bisimidazole-based HCV NS5A inhibitors bearing annulated tricyclic motifs

  • Bioorg Med Chem Lett. 2014 Dec 15;24(24):5738-5742. doi: 10.1016/j.bmcl.2014.10.056.
Min Zhong  1 ,  Eric Peng  2 ,  Ningwu Huang  2 ,  Qi Huang  2 ,  Anja Huq  2 ,  Meiyen Lau  2 ,  Richard Colonno  2 ,  Leping Li  3
Affiliations
  • 1. Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA. Electronic address: [email protected].
  • 2. Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
  • 3. Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA. Electronic address: [email protected].
PMID: 25453811 DOI: 10.1016/j.bmcl.2014.10.056
Abstract

This Letter describes the synthesis and biological evaluation of a number of functionalized bisimidazoles bearing annulated tricyclic motifs as potent inhibitors of HCV NS5A protein. Compound 4 h, which contains a substituted tricyclic 6-6-6 xanthene, demonstrated broad genotypic spectrum, compelling potency, and good oral bioavailability with dose-dependent drug exposure level in multiple animal species.

Keywords
Annulated tricyclic; Bisimidazole; HCV; NS5A inhibitor.