Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors

  • Bioorg Med Chem Lett. 2014 Dec 15;24(24):5731-5737. doi: 10.1016/j.bmcl.2014.10.057.
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: 25453810 DOI: 10.1016/j.bmcl.2014.10.057
Abstract

This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration.

Keywords
Bisimidazole; HCV; NS5A inhibitor.