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Despite decades of research, anticancer medication therapy is still largely constrained to prevent growth and limit the spread of tumour cells. To speed up the process of finding anticancer drugs, exploring novel therapeutic macromolecules and identifying the right small molecules using an integration of computational and experimental approaches is a recent tactic adopted by investigators. In the present study, we designed and created a library of 200 ligands with 3,4-dihydropyrimidinones or their thiones linked with imidazolidinones through amide linkage and explored the extent of their in vitro anticancer activity towards human topoisomerase IIalpha (TOP2α or TOP2A) using DU-145 and PC-3 prostate cancer cell lines using the SRB assay method. This was accomplished by the molecular docking and synthesis of the titled compounds using a series of organic nucleophilic addition reactions, including the Biginelli one-pot condensation reaction. The preliminary physical character evaluation was employed for the synthesized compounds, and the structural parameters were analyzed using FTIR, proton NMR, 13C NMR, and LC-MS/MS. The anti-prostate cancer activity of the prepared Biginelli analogues was evaluated against cancer cell lines and mild-to-moderate reduction in the viability of cell lines was observed with compounds 5, 6, 9, 14, 15, 16, 17, and 19. Among them, compounds 5, 14, 15, and 16 exhibited significant potent activity against TOP2α or TOP2A. This result indicated that the derivatives of Biginelli (3,4-dihydropyrimidinones/thiones) could be promising anti-prostate cancer drug candidates.

Despite decades of research, anticancer medication therapy is still largely constrained to prevent growth and limit the spread of tumour cells. To speed up the process of finding anticancer drugs, exploring novel therapeutic macromolecules and identifying the right small molecules using an integration of computational and experimental approaches is a recent tactic adopted by investigators. In the present study, we designed and created a library of 200 ligands with 3,4-dihydropyrimidinones or their thiones linked with imidazolidinones through amide linkage and explored the extent of their in vitro anticancer activity towards human topoisomerase IIalpha (TOP2α or TOP2A) using DU-145 and PC-3 prostate cancer cell lines using the SRB assay method. This was accomplished by the molecular docking and synthesis of the titled compounds using a series of organic nucleophilic addition reactions, including the Biginelli one-pot condensation reaction. The preliminary physical character evaluation was employed for the synthesized compounds, and the structural parameters were analyzed using FTIR, proton NMR, 13C NMR, and LC-MS/MS. The anti-prostate cancer activity of the prepared Biginelli analogues was evaluated against cancer cell lines and mild-to-moderate reduction in the viability of cell lines was observed with compounds 5 , 6 , 9 , 14 , 15 , 16 , 17, and 19. Among them, compounds 5 , 14 , 15 , and 16 exhibited significant potent activity against TOP2α or TOP2A. This result indicated that the derivatives of Biginelli (3,4-dihydropyrimidinones/thiones) could be promising anti-prostate cancer drug candidates. [ABSTRACT FROM AUTHOR]

The Biginelli reaction is an acid-catalyzed, three-component reaction between an aldehyde, a hydrogen methylene active compound, and urea (or its analogue) and constitutes a rapid and easy synthesis of highly functionalized heterocycles. Synthesis of ethyl 6-methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate, identified by our laboratory code LaSOM® 293, was achieved using the Biginelli reaction as the key step, followed by the Huisgen 1,3-dipolar cycloaddition in a convergent four-step route. The product LaSOM® 293 was obtained with a yield of 84%.

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An efficient synthesis of 3,4-dihydropyrimidinone derivatives using lanthanum oxide as a catalyst, from aldehydes, β-keto ester and urea/thiourea without solvent under the irradiation of microwave is described. Compared with classical Biginelli reaction conditions, this new method has the advantage of excellent yields and shorter reaction times.

In this method, we have reported the catalytic ability of saccharin as a green, eco-friendly catalyst for the multi-component efficient synthesis of 3,4-dihydropyrimidin-2-(1 H)-one derivatives and 1 H-pyrazolo [1,2- b]phthalazine-5,10-dione derivatives and substituted dihydro-2-oxypyrrole with excellent yields and short reaction times. This present methodology has notable benefits such as green, inexpensive and non-toxic catalyst, one-pot, environmental benign nature, solvent-free conditions, simplicity of operation with no necessity of chromatographic purification steps and eco-friendly. Graphical Abstract: We have studied the catalytic ability of saccharin as a green, economical and environmentally benign nature for the multi-component efficient synthesis of 3,4-dihydropyrimidin-2-(1 H)-ones derivatives, 1 H-pyrazolo[1,2- b]phthalazine-5,10-dione derivatives and substituted dihydro-2-oxypyrrole with excellent yields and short reaction times. Green catalyst, mild, non-toxic, inexpensive, simple operational procedures, one-pot, high catalytic activity, eco-friendly, easily separated from the reaction mixture with no column chromatographic for the one-pot multi-component synthesis of these compounds are the most important advantages of this procedure. [ABSTRACT FROM AUTHOR]

A new series of 4-aryl-6-methyl-5-(2-oxo-2 H -chromene-3-carbonyl)-3,4-dihydropyrimidin-2(1 H )-ones/thiones (DHPMs) have been synthesized through multicomponent Biginelli reactions, involving 3-(acetoacetyl)coumarin derivatives, para -substituted benzaldehydes, and urea/thiourea in refluxing acetonitrile, in the presence of a catalytic amount of sulfuric acid. The structure of all newly synthesized compounds has been established by 2D NMR spectroscopic spectra (HSQC, HMBC, and NOESY), elemental analysis, and mass spectrometry. [ABSTRACT FROM AUTHOR]

A novel effective synthesis of 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives, using conducting polyaniline (PANI) as a catalyst from aldehydes, β-ketoester and urea under solvent free conditions has been described. The effect of organic solvents on the human body and the environment is hazardous and its disposal is a major problem. Hence, solvent less organic reaction have attracted attention of chemists. Solvent free solid-state reaction carried out using the reactant alone reduces the pollution, and is more economical and environment friendly. PANI catalyst and solvent free condition reduces the side reactions that occur in other protonated acid media. The use of the sonochemical method is a green route for the synthesis of dihydropyrimidinones (DHPM). Compared with the traditional reaction, this method has the advantage of shorter reaction time with excellent yield, purity of DHPM and low loading of raw materials. Polyaniline is a mild, stable, recyclable, cheaper and highly efficient catalyst and used several times with excellent yield for the dihydropyrimidinone synthesis. Polyaniline (PANI) was characterized by UV-Visible, FTIR, XRD and SEM studies. DHPM were characterized by NMR, MS and IR spectroscopy. In the present paper, a green approach for the synthesis of dihydropyrimidinone assisted by polyaniline as a catalyst under solvent-free conditions is reported. [ABSTRACT FROM PUBLISHER]

Abstract: For the first time hexaaquaaluminium(III) tetrafluoroborate has been used as a mild acid catalyst in organic synthesis. A simple method of its preparation based on the reaction of aluminium triisopropoxide and tetrafluoroboric acid in isopropanol afforded catalyst of high purity and activity. The three-component Biginelli condensation of acetoacetate esters, urea and aldehydes catalyzed by 10mol% of [Al(H2O)6](BF4)3 in refluxing acetonitrile afforded 3,4-dihydropyrimidonones in good to high yields on multigram scales. The tolerance to acid sensitive reactants such as thienyl and furyl carbaldehydes, applicability to sterically hindered β-ketoesters and simple recyclability without losing catalytic activity make this catalyst as good replacement to literature methods. The mechanism of the reaction includes formation of the so called ‘ureido-crotonate’ rather than corresponding acylimino intermediate as found with Brønsted type catalysts. [Copyright &y& Elsevier]

2-Mercaptoquinoline substituted 1,2,3,4-tetrahydropyrimidinones have been efficiently synthesized in high yields in a short reaction time using TiCl3 as catalyst, in THF solvent. The mechanism is proposed based on the presence of Lewis acid catalyst in Biginelli condensation. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of 3,4-dihydropyrimidinone derivatives was achieved in good to excellent yields using phenylboronic acid as catalyst to promote the Biginelli three-component condensation of a diversity of aromatic aldehydes, ethyl acetoacetate and urea or thiourea. [Copyright &y& Elsevier]

The Biginelli reaction is an acid-catalyzed, three-component reaction between an aldehyde, a hydrogen methylene active compound, and urea (or its analogue) and constitutes a rapid and easy synthesis of highly functionalized heterocycles. Synthesis of ethyl 6-methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate, identified by our laboratory code LaSOM® 293, was achieved using the Biginelli reaction as the key step, followed by the Huisgen 1,3-dipolar cycloaddition in a convergent four-step route. The product LaSOM® 293 was obtained with a yield of 84%. [ABSTRACT FROM AUTHOR]

An efficient synthesis of 3,4-dihydropyrimidinone derivatives using lanthanum oxide as a catalyst, from aldehydes, β-keto ester and urea/thiourea without solvent under the irradiation of microwave is described. Compared with classical Biginelli reaction conditions, this new method has the advantage of excellent yields and shorter reaction times. [ABSTRACT FROM AUTHOR]