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

doi:10.3390/molecules25184152

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

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

¹,

²,

¹,

¹,

¹ and

^1,*

Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, via Licio Giorgieri 1, 34127 Trieste, Italy

Dipartimento di Scienze, Università della Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, Italy

Author to whom correspondence should be addressed.

Academic Editor: Florenci V. González

Molecules 2020, 25(18), 4152; https://doi.org/10.3390/molecules25184152

Received: 30 July 2020 / Revised: 31 August 2020 / Accepted: 2 September 2020 / Published: 10 September 2020

(This article belongs to the Special Issue Organic Synthesis in Natural Products and Bioactive Compounds)

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

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 IC₅₀ in the range 100 nM–50 μM. View Full-Text

Keywords: Alzheimer’s disease; dihydropyrimidinones; Biginelli reaction; β-secretase; BACE-1 inhibitors

▼ Show Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
PDF-Document (PDF, 1171 KiB)

Share and Cite

MDPI and ACS Style

Bais, J.; Benedetti, F.; Berti, F.; Cerminara, I.; Drioli, S.; Funicello, M.; Regini, G.; Vidali, M.; Felluga, F. One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues. Molecules 2020, 25, 4152. https://doi.org/10.3390/molecules25184152

AMA Style

Bais J, Benedetti F, Berti F, Cerminara I, Drioli S, Funicello M, Regini G, Vidali M, Felluga F. One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues. Molecules. 2020; 25(18):4152. https://doi.org/10.3390/molecules25184152

Chicago/Turabian Style

Bais, Jessica, Fabio Benedetti, Federico Berti, Iole Cerminara, Sara Drioli, Maria Funicello, Giorgia Regini, Mattia Vidali, and Fulvia Felluga. 2020. "One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues" Molecules 25, no. 18: 4152. https://doi.org/10.3390/molecules25184152

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

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

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI