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Potent bisimidazole-based HCV NS5A inhibitors bearing annulated tricyclic motifs.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Dec 15; Vol. 24 (24), pp. 5738-5742. Date of Electronic Publication: 2014 Oct 22. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antiviral Agents chemical synthesis
Antiviral Agents pharmacokinetics
Cyclization
Dogs
Genotype
Half-Life
Haplorhini
Hepacivirus genetics
Imidazoles chemical synthesis
Imidazoles pharmacokinetics
Rats
Structure-Activity Relationship
Viral Nonstructural Proteins metabolism
Xanthenes chemical synthesis
Xanthenes pharmacokinetics
Antiviral Agents chemistry
Hepacivirus metabolism
Imidazoles chemistry
Viral Nonstructural Proteins antagonists & inhibitors
Xanthenes chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 24
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 25453811
- Full Text :
- https://doi.org/10.1016/j.bmcl.2014.10.056