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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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
Descripción
Sumario: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.