Exploring the N1 Position of Biginelli Compounds: New Insights and Trends for Chemical Diversity Generation of Bioactive Derivatives

: Dihydropyrimidinones (DHPMs) are heterocycles obtained by the multicomponent Biginelli reaction. Recently, new synthetic protocols have allowed us to explore functionalisation at less explored positions of DHPMs, such as the N1 position. In this context, we have performed a full literature survey of N1-substituted DHPMs. We analysed 27 papers and identified 379 compounds with substituents at the N1 position, most of them with alkyl groups, and of 28% with aromatic substituents attached at the N1 position. N1-substituted DHPMs are explored mainly due to their effects on cancer cell proliferation via numerous targets, such as kinesin Eg5, heat shock protein 70, heat shock protein 90 and the epidermal growth factor receptor. Similarity analyses were performed using the data of 379 DHPMs from different cheminformatic approaches, i.e. chemical property correlations, principal component analysis, similarity networks and compound clustering.

New Strategy for Synthesis of Anticancer Active Piperastrol, Enastron using Ammonium Sulfocyanate

This report describes an efficient and mild approach for the synthesis of Piperastrol and Enastron via a one-pot three-component cyclocondensation reaction employing ammonium sulfocyanate (NH4SCN) on gram scale in isopropyl alcohol–PEG 400 medium. In this reaction ammonium sulfocyanate is not only one of the reacting components, but also accelerates the rate of reaction to afford Biginelli compounds. High yields, short reaction time and easy workup procedure are the key advantages of the present protocol. Ammonium sulfocyanate is readily available, cheaper, safer and industrial acceptable inorganic salt.

Biginelli Synthesis of Novel Dihydropyrimidinone Derivatives Containing Phthalimide Moiety

A new series of novel Biginelli compounds, 5-benzoyl-substituted phenyl-3,4-dihydropyrimidin-2(1H)-one-1H-isoindole-1,3(2H)-dione (1−10), were synthesized from enaminone, 2-{4-[(2E)-3-(dimethylamino)prop-2-enoyl]phenyl}-1H-isoindole-1,3(2H)-dione (IV), which was synthesized by refluxing 2-(4-acetylphenyl)-1H-isoindole-1,3(2H)-dione (III), with dimethylformamide-dimethylacetal (DMF-DMA) without solvent for 12 h. The compound 2-(4-acetylphenyl)-1H-isoindole-1,3(2H)-dione (III) was obtained by reacting phthalic anhydride (I) with para-aminoacetophenone (II) in glacial acetic acid for 2 h. The dihydropyrimidinone derivatives containing phthalimide moiety (1–10) were obtained by reacting enaminone, 2-{4-[(2E)-3-(dimethylamino) prop-2-enoyl] phenyl}-1H-isoindole-1,3(2H)-dione (IV), with urea and different substituted benzaldehydes in the presence of glacial acetic acid for 3 h. Simple and efficient method was employed to synthesize the dihydropyrimidinone derivatives containing phthalimide moiety. Structures of all the synthesized compounds were characterized by spectroscopic methods.

Hybrid 3,4-dihydropyrimidin-2-(thi)ones as dual-functional bioactive molecules: fluorescent probes and cytotoxic agents to cancer cells

A series of new hybrid fluorescent Biginelli compounds, including a Monastrol derivative, were designed and synthesized with good yields.

Reduction of Biginelli compounds by LiAlH4: a rapid access to molecular diversity

The reduction of Biginelli compounds by LiAlH4 provides a rapid access to molecular diversity.

Titanium dioxide supported on MWCNTs as an eco-friendly catalyst in the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones accelerated under microwave irradiation

Some transition metal oxides supported on MWCNTs were prepared as novel heterogeneous catalysts using the facile processes. These catalysts were used for the synthesis of Biginelli compounds under microwave irradiation.