2. Academic Validation
  3. Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors

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

Affiliations

  • 1 Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA. Electronic address: min.zhong@acmeca.com.
  • 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: lli@presidiopharma.com.
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.

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