title: Potent bisimidazole-based HCV NS5A inhibitors bearing annulated tricyclic motifs.
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.
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 / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003500:Cyclization; D004285:Dogs; D005838:Genotype; D006207:Half-Life; D000882:Haplorhini; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014966:Xanthenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007093:Imidazoles; D017361:Viral Nonstructural Proteins; D014966:Xanthenes; C029899:imidazole; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Annulated tricyclic; Bisimidazole; HCV; NS5A inhibitor