title: An efficient new route to dihydropyranobenzimidazole inhibitors of HCV replication.
abstract: A class of dihydropyranobenzimidazole inhibitors was recently discovered that acts against the hepatitis C virus (HCV) in a new way, binding to the IRES-IIa subdomain of the highly conserved 5' untranslated region of the viral RNA and thus preventing the ribosome from initiating translation. However, the reported synthesis of these compounds is lengthy and low-yielding, the intermediates are troublesome to purify, and the route is poorly structured for the creation of libraries. We report a streamlined route to this class of inhibitors in which yields are far higher and most intermediates are crystalline. In addition, a key variable side chain is introduced late in the synthesis, allowing analogs to be easily synthesized for optimization of antiviral activity.
authors.affiliation: Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182, USA. parker@sciences.sdsu.edu
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Parker
authors.forename: Emily
authors.initials: E
authors.lastname: Satkiewicz
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
authors.forename: B Mikael
authors.initials: BM
authors.lastname: Bergdahl
mesh_terms: D020121:5' Untranslated Regions; D000998:Antiviral Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D020121:5' Untranslated Regions; D000998:Antiviral Agents; D001562:Benzimidazoles