Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()

The results of a high-throughput screening assay using the dengue virus-2 replicon showed that the imidazole 4,5-dicarboxamide (I45DC) derivative (15a) has a high dengue virus inhibitory activity. Based on 15a as a lead compound, a novel class of both disubstituted I45DCs and the resembling pyrazine...

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Autores principales: Saudi, Milind, Zmurko, Joanna, Kaptein, Suzanne, Rozenski, Jef, Neyts, Johan, Van Aerschot, Arthur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Editions Scientifiques Elsevier 2014
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237513/
https://www.ncbi.nlm.nih.gov/pubmed/25285371
http://dx.doi.org/10.1016/j.ejmech.2014.09.062
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author Saudi, Milind
Zmurko, Joanna
Kaptein, Suzanne
Rozenski, Jef
Neyts, Johan
Van Aerschot, Arthur
author_facet Saudi, Milind
Zmurko, Joanna
Kaptein, Suzanne
Rozenski, Jef
Neyts, Johan
Van Aerschot, Arthur
author_sort Saudi, Milind
collection PubMed
description The results of a high-throughput screening assay using the dengue virus-2 replicon showed that the imidazole 4,5-dicarboxamide (I45DC) derivative (15a) has a high dengue virus inhibitory activity. Based on 15a as a lead compound, a novel class of both disubstituted I45DCs and the resembling pyrazine 2,3-dicarboxamides (P23DCs) were synthesized. Here, we report on their in vitro inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Some of these first generation compounds have shown activity against both viruses in the micromolar range. Within this series, compound 15b was observed to display the highest antiviral potency against YFV with an EC(50) = 1.85 μM. In addition, compounds 20a and 20b both potently inhibited replication of DENV (EC(50) = 0.93 μM) in Vero cells.
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spelling pubmed-42375132014-11-25 Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus() Saudi, Milind Zmurko, Joanna Kaptein, Suzanne Rozenski, Jef Neyts, Johan Van Aerschot, Arthur Eur J Med Chem Original Article The results of a high-throughput screening assay using the dengue virus-2 replicon showed that the imidazole 4,5-dicarboxamide (I45DC) derivative (15a) has a high dengue virus inhibitory activity. Based on 15a as a lead compound, a novel class of both disubstituted I45DCs and the resembling pyrazine 2,3-dicarboxamides (P23DCs) were synthesized. Here, we report on their in vitro inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Some of these first generation compounds have shown activity against both viruses in the micromolar range. Within this series, compound 15b was observed to display the highest antiviral potency against YFV with an EC(50) = 1.85 μM. In addition, compounds 20a and 20b both potently inhibited replication of DENV (EC(50) = 0.93 μM) in Vero cells. Editions Scientifiques Elsevier 2014-11-24 /pmc/articles/PMC4237513/ /pubmed/25285371 http://dx.doi.org/10.1016/j.ejmech.2014.09.062 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) .
spellingShingle Original Article
Saudi, Milind
Zmurko, Joanna
Kaptein, Suzanne
Rozenski, Jef
Neyts, Johan
Van Aerschot, Arthur
Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()
title Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()
title_full Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()
title_fullStr Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()
title_full_unstemmed Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()
title_short Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()
title_sort synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus()
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237513/
https://www.ncbi.nlm.nih.gov/pubmed/25285371
http://dx.doi.org/10.1016/j.ejmech.2014.09.062
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