Discovery of 3,4-Dihydropyrimidin-2(1<i>H</i>)-ones As a Novel Class of Potent and Selective A<sub>2B</sub> Adenosine Receptor Antagonists

Crespo, Abel; Maatougui, Abdelaziz El; Biagini, Pierfrancesco; Azuaje, Jhonny; Coelho, Alberto; Brea, José; Loza, Marı́a Isabel; Cadavid, Marı́a Isabel; Garcı́a-Mera, Xerardo; Gutiérrez‐de‐Terán, Hugo; Sotelo, Eddy

doi:10.1021/ml400185v

Cited by 65 publications

(121 citation statements)

References 31 publications

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“…5-Ethoxycarbonyl-4-(4-fluorophenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-thione 3b [ 46 ]. From 4-fluorobenzaldehyde, ethylacetoacetate, thiourea; 0.200 g, 68%, light yellow solid, m.p.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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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.

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“…5-Ethoxycarbonyl-4-(4-fluorophenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-thione 3b [ 46 ]. From 4-fluorobenzaldehyde, ethylacetoacetate, thiourea; 0.200 g, 68%, light yellow solid, m.p.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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“…1) have large biological activities and many synthetic samples have been studied as calcium channel modulators, mitotic kinesin inhibitors, adrenergic receptor antagonists, antibacterials, antivirals, and others. 17,18 Some natural products containing DHPM moiety have been studied as new leads for AIDS therapies.…”

Section: Introduction *mentioning

confidence: 99%

Biginelli reaction via bis-ureide intermediate in low melting mixture

Mahajan¹,

JAMWAL²,

Paul³

2019

Rev.Roum.Chim.

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This paper deals with the study of mechanism of the Biginelli reaction using low melting mixture as solvent and catalyst. The catalytic effect of low melting mixture and the reaction mechanism is discussed on the basis of nuclear magnetic resonance (NMR) and mass spectrometry (ESI-MS). All experimental measurements point to a mechanism involving bis-ureide derivative as a key intermediate, formed by the reaction of benzaldehyde and urea in low melting mixture.

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“…DHPMs usually have distinct biological activities and can be applied as calcium channel modulators, adrenergic receptor antagonists, antibacterials, mitotic Kinesin inhibitors, antivirals, and others, as reviewed elsewhere. [25][26][27] Importantly, DHPMs typically have pronounced biological activities in their racemic forms, 28 In this context, the courtship between CPs/MOFs and MCRs has produced promising results which opened up a large but as yet unexploited avenue of possibilities. Some MCRs, for instance, have been recently performed catalysed by CPs/MOF scaffolds with relative successes; 29-31 therefore fostering interest in the development of new stable and more robust hybrid materials capable of performing catalysed MCRs.…”

Section: Introductionmentioning

confidence: 99%

The Biginelli reaction under batch and continuous flow conditions: catalysis, mechanism and antitumoral activity

et al. 2015

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Two novel coordination polymers (CPs) have been synthesized, characterized and successfully applied as robust heterogeneous catalysts for the Biginelli multicomponent reaction to obtain 3,4dihydropyrimidin-2(1H)-one or thione (DHPMs) derivatives. The reaction was initially developed using both CPs and the Zn-based material showed much better catalytic activity. After the reaction optimization under batch conditions, a continuous flow protocol was developed and applied with impressive results. Four bioactive DHPMs were successfully synthesized with high yields. The mechanism of the transformation was also investigated by electrospray (tandem) mass spectrometry (ESI-MS(/MS)) analyses. Online monitoring of the reaction indicated under the developed conditions that the iminium mechanism is preferred over the enamine-and Knoevenagel-based mechanisms. Nine DHPMs had their antitumoral activities evaluated against MCF-7 (human breast cancer cells), A549 (human alveolar basal epithelial cells) and Caco-2 (human epithelial colorectal cells) cancer cell lineages. Fibroblasts (healthy cells) were not affected by the tested DHPMs showing an excellent selectivity for tumour cells. Three DHPMs returned impressive results, being capable of inhibiting tumour cell proliferation in 72 h.

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Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and Selective A_2B Adenosine Receptor Antagonists

Cited by 65 publications

References 31 publications

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

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

Biginelli reaction via bis-ureide intermediate in low melting mixture

The Biginelli reaction under batch and continuous flow conditions: catalysis, mechanism and antitumoral activity

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Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and Selective A2B Adenosine Receptor Antagonists

Cited by 65 publications

References 31 publications

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

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

Biginelli reaction via bis-ureide intermediate in low melting mixture

The Biginelli reaction under batch and continuous flow conditions: catalysis, mechanism and antitumoral activity

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Product

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Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and Selective A_2B Adenosine Receptor Antagonists