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An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity
In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desir...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018746/ https://www.ncbi.nlm.nih.gov/pubmed/32054916 http://dx.doi.org/10.1038/s41598-020-59079-z |
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author | Peytam, Fariba Adib, Mehdi Shourgeshty, Reihaneh Firoozpour, Loghman Rahmanian-Jazi, Mahmoud Jahani, Mehdi Moghimi, Setareh Divsalar, Kouros Faramarzi, Mohammad Ali Mojtabavi, Somayeh Safari, Fatemeh Mahdavi, Mohammad Foroumadi, Alireza |
author_facet | Peytam, Fariba Adib, Mehdi Shourgeshty, Reihaneh Firoozpour, Loghman Rahmanian-Jazi, Mahmoud Jahani, Mehdi Moghimi, Setareh Divsalar, Kouros Faramarzi, Mohammad Ali Mojtabavi, Somayeh Safari, Fatemeh Mahdavi, Mohammad Foroumadi, Alireza |
author_sort | Peytam, Fariba |
collection | PubMed |
description | In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC(50) values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC(50) = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones. |
format | Online Article Text |
id | pubmed-7018746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70187462020-02-21 An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity Peytam, Fariba Adib, Mehdi Shourgeshty, Reihaneh Firoozpour, Loghman Rahmanian-Jazi, Mahmoud Jahani, Mehdi Moghimi, Setareh Divsalar, Kouros Faramarzi, Mohammad Ali Mojtabavi, Somayeh Safari, Fatemeh Mahdavi, Mohammad Foroumadi, Alireza Sci Rep Article In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC(50) values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC(50) = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones. Nature Publishing Group UK 2020-02-13 /pmc/articles/PMC7018746/ /pubmed/32054916 http://dx.doi.org/10.1038/s41598-020-59079-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Peytam, Fariba Adib, Mehdi Shourgeshty, Reihaneh Firoozpour, Loghman Rahmanian-Jazi, Mahmoud Jahani, Mehdi Moghimi, Setareh Divsalar, Kouros Faramarzi, Mohammad Ali Mojtabavi, Somayeh Safari, Fatemeh Mahdavi, Mohammad Foroumadi, Alireza An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity |
title | An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity |
title_full | An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity |
title_fullStr | An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity |
title_full_unstemmed | An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity |
title_short | An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity |
title_sort | efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018746/ https://www.ncbi.nlm.nih.gov/pubmed/32054916 http://dx.doi.org/10.1038/s41598-020-59079-z |
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