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5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production
A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier–Haack–Arnold reagent, followed by immediate deprotect...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080047/ https://www.ncbi.nlm.nih.gov/pubmed/32214763 http://dx.doi.org/10.1007/s00044-014-1018-9 |
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author | Jansa, Petr Holý, Antonín Dračínský, Martin Kolman, Viktor Janeba, Zlatko Kostecká, Petra Kmoníčková, Eva Zídek, Zdeněk |
author_facet | Jansa, Petr Holý, Antonín Dračínský, Martin Kolman, Viktor Janeba, Zlatko Kostecká, Petra Kmoníčková, Eva Zídek, Zdeněk |
author_sort | Jansa, Petr |
collection | PubMed |
description | A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier–Haack–Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6-dichloropyrimidine with an IC (50) of 2 µM (higher activity than the most potent reference compound) while the IC (50)s of other derivatives were within the range of 9–36 µM. The 2-amino-4,6-dihydroxypyrimidine counterparts were devoid of any NO-inhibitory activity. The compounds had no suppressive effects on the viability of cells. The Mechanism of action remains to be elucidated. |
format | Online Article Text |
id | pubmed-7080047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-70800472020-03-23 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production Jansa, Petr Holý, Antonín Dračínský, Martin Kolman, Viktor Janeba, Zlatko Kostecká, Petra Kmoníčková, Eva Zídek, Zdeněk Med Chem Res Original Research A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier–Haack–Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6-dichloropyrimidine with an IC (50) of 2 µM (higher activity than the most potent reference compound) while the IC (50)s of other derivatives were within the range of 9–36 µM. The 2-amino-4,6-dihydroxypyrimidine counterparts were devoid of any NO-inhibitory activity. The compounds had no suppressive effects on the viability of cells. The Mechanism of action remains to be elucidated. Springer US 2014-05-09 2014 /pmc/articles/PMC7080047/ /pubmed/32214763 http://dx.doi.org/10.1007/s00044-014-1018-9 Text en © Springer Science+Business Media New York 2014 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Research Jansa, Petr Holý, Antonín Dračínský, Martin Kolman, Viktor Janeba, Zlatko Kostecká, Petra Kmoníčková, Eva Zídek, Zdeněk 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production |
title | 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production |
title_full | 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production |
title_fullStr | 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production |
title_full_unstemmed | 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production |
title_short | 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production |
title_sort | 5-substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080047/ https://www.ncbi.nlm.nih.gov/pubmed/32214763 http://dx.doi.org/10.1007/s00044-014-1018-9 |
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