An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2011 Jan 4

PMID 21193848

Citations 8

Authors

Matthew A Parker

Emily Satkiewicz

Thomas Hermann

B Mikael Bergdahl

Affiliations

Soon will be listed here.

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.

Citing Articles

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Small molecules targeting viral RNA.

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Conformational flexibility of viral RNA switches studied by FRET.

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Functional conservation despite structural divergence in ligand-responsive RNA switches.

Boerneke M, Dibrov S, Gu J, Wyles D, Hermann T Proc Natl Acad Sci U S A. 2014; 111(45):15952-7.

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Hepatitis C virus translation inhibitors targeting the internal ribosomal entry site.

Dibrov S, Parsons J, Carnevali M, Zhou S, Rynearson K, Ding K J Med Chem. 2013; 57(5):1694-707.

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