One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues

A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydroc...

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Autores principales: Bais, Jessica, Benedetti, Fabio, Berti, Federico, Cerminara, Iole, Drioli, Sara, Funicello, Maria, Regini, Giorgia, Vidali, Mattia, Felluga, Fulvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571164/
https://www.ncbi.nlm.nih.gov/pubmed/32927879
http://dx.doi.org/10.3390/molecules25184152
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author Bais, Jessica
Benedetti, Fabio
Berti, Federico
Cerminara, Iole
Drioli, Sara
Funicello, Maria
Regini, Giorgia
Vidali, Mattia
Felluga, Fulvia
author_facet Bais, Jessica
Benedetti, Fabio
Berti, Federico
Cerminara, Iole
Drioli, Sara
Funicello, Maria
Regini, Giorgia
Vidali, Mattia
Felluga, Fulvia
author_sort Bais, Jessica
collection PubMed
description A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC(50) in the range 100 nM–50 μM.
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spelling pubmed-75711642020-10-28 One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues Bais, Jessica Benedetti, Fabio Berti, Federico Cerminara, Iole Drioli, Sara Funicello, Maria Regini, Giorgia Vidali, Mattia Felluga, Fulvia Molecules Article A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC(50) in the range 100 nM–50 μM. MDPI 2020-09-10 /pmc/articles/PMC7571164/ /pubmed/32927879 http://dx.doi.org/10.3390/molecules25184152 Text en © 2020 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 (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bais, Jessica
Benedetti, Fabio
Berti, Federico
Cerminara, Iole
Drioli, Sara
Funicello, Maria
Regini, Giorgia
Vidali, Mattia
Felluga, Fulvia
One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
title One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
title_full One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
title_fullStr One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
title_full_unstemmed One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
title_short One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
title_sort one pot synthesis of micromolar bace-1 inhibitors based on the dihydropyrimidinone scaffold and their thia and imino analogues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571164/
https://www.ncbi.nlm.nih.gov/pubmed/32927879
http://dx.doi.org/10.3390/molecules25184152
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