title: Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors.
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.
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA. Electronic address: min.zhong@acmeca.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Peng
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors.forename: Ningwu
authors.initials: N
authors.lastname: Huang
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Huq
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors.forename: Meiyen
authors.initials: M
authors.lastname: Lau
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Colonno
authors.affiliation: Presidio Pharmaceuticals, Inc., 1700 Owens Street, Suite 585, San Francisco, CA 94158, USA. Electronic address: lli@presidiopharma.com.
authors.forename: Leping
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000821:virology; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D006839:Hydrocarbons, Acyclic / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000821:virology; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012093:Replicon / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D006839:Hydrocarbons, Acyclic; D007093:Imidazoles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Bisimidazole; HCV; NS5A inhibitor