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An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication

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. Ho...

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Detalles Bibliográficos
Autores principales: Parker, Matthew A., Satkiewicz, Emily, Hermann, Thomas, Bergdahl, B. Mikael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259416/
https://www.ncbi.nlm.nih.gov/pubmed/21193848
http://dx.doi.org/10.3390/molecules16010281
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author Parker, Matthew A.
Satkiewicz, Emily
Hermann, Thomas
Bergdahl, B. Mikael
author_facet Parker, Matthew A.
Satkiewicz, Emily
Hermann, Thomas
Bergdahl, B. Mikael
author_sort Parker, Matthew A.
collection PubMed
description 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.
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spelling pubmed-62594162018-12-07 An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication Parker, Matthew A. Satkiewicz, Emily Hermann, Thomas Bergdahl, B. Mikael Molecules Article 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. MDPI 2010-12-30 /pmc/articles/PMC6259416/ /pubmed/21193848 http://dx.doi.org/10.3390/molecules16010281 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Parker, Matthew A.
Satkiewicz, Emily
Hermann, Thomas
Bergdahl, B. Mikael
An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication
title An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication
title_full An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication
title_fullStr An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication
title_full_unstemmed An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication
title_short An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication
title_sort efficient new route to dihydropyranobenzimidazole inhibitors of hcv replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259416/
https://www.ncbi.nlm.nih.gov/pubmed/21193848
http://dx.doi.org/10.3390/molecules16010281
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