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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated a critical need for treatments to reduce morbidity and mortality associated with this disease. However, traditional drug development takes many years, which is not practical solution given the current pandemic. Therefore, a viable option is to repurpose existing drugs. The structural data of several proteins vital for the virus became available shortly after the start of the pandemic. In this review, we discuss the importance of these targets and their available potential inhibitors predicted by the computational approaches. Among the hits identified by computational approaches, 35 candidates were suggested for further evaluation, among which ten drugs are in clinical trials (Phase III and IV) for treating Coronavirus 2019 (COVID-19).

The title complex, systematic name catena-poly[[[acetatochloridozinc(II)]-μ-(5R,6R,7S)-5-(furan-2-yl)-7-phenyl-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidin-6-amine] monohydrate], {[Zn(C2H3O2)Cl(C15H15N5O)]·H2O} n , is the first coordination complex in which the neutral tetrahydrotriazolopyrimidine derivative acts as bridging ligand between two zinc molecules. As a result, polymeric chains of the coordination complex are found. The coordination of the zinc metal atom occurs with the lone pairs of the triazolo nitrogen atom and amino group. The positive charge of the zinc atom is compensated by the chlorine anion and deprotonated acetic acid. The coordination complex exists as a monohydrate in the crystalline phase. The water molecules bind neighbouring polymeric chains by the formation of O—H...O, O—H...Cl and N—H...O hydrogen bonds.

For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an essential enzyme that catalyses the replication from RNA template and therefore remains an attractive therapeutic target for anti-COVID drug discovery. In the present study, we performed a comprehensive

The unexpectedly uncatalyzed reaction between 2-amino-4-arylimidazoles, aromatic aldehydes and Meldrum’s acid has selectively led to the corresponding Knoevenagel–Michael adducts containing a free amino group in the imidazole fragment. The adducts derived from Meldrum’s acid have been smoothly converted into 1,7-diaryl-3-amino-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-ones and 3-(2-amino-4-aryl-1H-imidazol-5-yl)-3-arylpropanoic acids. The interaction of 2-amino-4-arylimidazoles with aromatic aldehydes or isatins and acyclic methylene active compounds has led to the formation of pyrrolo[1,2-c]imidazole-6-carbonitriles, pyrrolo[1,2-с]imidazole-6-carboxylates and spiro[indoline-3,7'-pyrrolo[1,2-c]imidazoles], which can be considered as the analogues of both 3,3’-spirooxindole and 2-aminoimidazole marine sponge alkaloids.

For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an essential enzyme that catalyses the replication from RNA template and therefore remains an attractive therapeutic target for anti-COVID drug discovery. In the present study, we performed a comprehensive in silico screening for 16,776 potential molecules from recently established drug libraries based on two important pharmacophores (3-amino-4-phenylbutan-2-ol and piperazine). Based on initial assessment, 4042 molecules were obtained suitable as drug candidates, which were following Lipinski’s rule. Molecular docking implemented for the analysis of molecular interactions narrowed this number of compounds down to 19. Subsequent to screening filtering criteria and considering the critical parameters viz. docking score and MM-GBSA binding free energy, 1-(4-((2S,3S)-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea (compound 1) was accomplished to score highest in comparison to the remaining 18 shortlisted drug candidates. Notably, compound 1 displayed higher docking score (−8.069 kcal/mol) and MM-GBSA binding free energy (−49.56 kcal/mol) than the control drug, remdesivir triphosphate, the active form of remdesivir as well as adenosine triphosphate. Furthermore, a molecular dynamics simulation was carried out (100 ns), which substantiated the candidacy of compound 1 as better inhibitor. Overall, our systematic in silico study predicts the potential of compound 1 to exhibit a more favourable specific activity than remdesivir triphosphate. Hence, we suggest compound 1 as a novel potential drug candidate, which should be considered for further exploration and validation of its potential against SARS-CoV-2 in wet lab experimental studies. Communicated by Ramasawamy H. Sarma

The molecular structure of 7-methoxy-5-methyl-2-(pyridin-3-yl)-11,12-dihydro-5,11-methano[1,2,4]triazolo[1,5-c][1,3,5]benzoxadiazocine that formulated as (C18H17N5O2) was determined by single-crystal X-ray diffraction and FT-IR spectroscopy. The crystal structure is triclinic, space group P-1 with parameters a = 10.0175(7) A, b = 9.9702(6) A, c = 17.5941(10) A, α = 96.546(5)˚, β = 106.069(5)˚, γ = 97.178(5)˚, V = 1654.87(19) A3, Z = 4. Theoretical calculations have been carried out by using Hartree-Fock (HF) and Density Functional Theory (DFT) methods. The vibrational frequencies were calculated by using HF/6-31G(d,p) and DFT/B3LYP/6-31G(d,p) basis sets in ground state. The calculated structural parameters (bond lengths, bond angles, torsion angles) and vibrational assignments were compared with their experimental data. Molecular Electrostatic Potential (MEP) map of the compound was obtained by using the optimized structures. Furthermore, the frontier molecular orbitals have been created for the compound. Crystal Explorer program was used to determine remarkable interactions in the crystal.

Identification of new small molecules inhibiting protein kinase CK2 is highly required for the study of this protein's functions in cell and for the further development of novel pharmaceuticals against a variety of disorders associated with CK2 activity. In this article, a virtual screening of a random small-molecule library was performed and 12 compounds were initially selected for biochemical tests toward CK2. Among them, the most active compound 1 ([Formula: see text]) belonged to dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-ones. The complex of this compound with CK2 was analyzed, and key ligand-enzyme interactions were determined. Then, a virtual screening of 231 dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-one derivatives was performed and 37 compounds were chosen for in vitro testing. It was found that 32 compounds inhibit CK2 with [Formula: see text] values from 2.5 to 7.5 [Formula: see text]. These results demonstrate that dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-one is a novel class of CK2 inhibitors.

Dege, Necmi/0000-0003-0660-4721; Aydemir, Ercan/0000-0003-0793-6576; Gumus, Mustafa Kemal/0000-0001-6373-5221; Kansiz, Sevgi/0000-0002-8433-7975 WOS: 000426268200022 PubMed: 29765725 The title compound, Ci(9)H(19)N(5)O(2), was prepared by the reaction of 3-amino-5(pyridin-3-yl)-1,2,4-triazole with acetone and 2-hydroxy-3-ethoxybenzaldehyde. It crystallizes from ethanol in a tetragonal space group, with one molecule in the asymmetric unit. The 1,2,4-triazole five-membered ring is planar (maximum deviation = 0.0028 angstrom). The pyridine and phenyl rings are also planar with maximum deviations of 0.0091 and 0.0094 angstrom, respectively. In the crystal, N-H center dot center dot center dot N hydrogen bonds link the molecules into supramolecular chains propagating along the c-axis direction. Hirshfeld surface analysis and twodimensional fingerprint plots have been used to analyse the intermolecular interactions present in the crystal. University Research Fund [F.279] The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mars University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund).

A microwave-assisted Biginelli-like three-component condensation using salicylic aldehyde derivatives, acetone, and 5-substituted 3-amino-1,2,4-triazoles instead of the urea component results in the formation of oxygen-bridged tetrahydrotriazolopyrimidine derivatives (11,12-dihydro-5,11-methano[1,2,4]triazolo[1,5-c][1,3,5]benzoxadiazocines) in good yields and high purity. A plausible reaction mechanism for this transformation is discussed in details using literature and experimental data.

A new class of chiral phthalimides functionalized with aryl piperazines was designed anticipating their strong candidature for crystal engineering and technological applications. Five new phthalimides were synthesized, characterized and subjected to single crystal X-ray diffraction study that directed their non-centrosymmetric structures. Four phthalimides crystallized in P21 space group with monoclinic crystal system, however, one was found to possess P212121 space group with orthorhombic system. The supramolecular architectures of phthalimide crystals were analysed by an approach based on consideration of energy of intermolecular interaction. The molecular hyperpolarizability (β) calculation for all the listed phthalimides indicated their promising candidature for NLO materials. Further, the crystalline form of all phthalimides was evaluated for their second harmonic generation (SHG) response. A significant response of 16.4 mV was measured for phthalimide possessing t-butyl substituent at the para position of 4-benzylpiperazine. This high SHG response may be attributed to the molecular chirality and helical supramolecular frameworks stabilized by C-H ⋯O hydrogen bonds in the solid state. The current study attests chiral phthalimides possessing arylpiperazines as effective nominees to the area of crystal engineering and nonlinear optics.

The new 2-amino-3-R-4-aryl-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine 5,5-dioxides were synthesized via three-component interaction of 1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with arylcarbaldehydes and active methylene nitriles. Depending on the nature of an active methylene nitrile and an arylcarbaldehyde this interaction can lead either to the target 2-amino-4H-pyrans or to the stable triethylammonium salts of bis(1H-2,1-benzothiazin-4(3H)-one 2,2-dioxides) (bis-adducts). The latter is a completely new product of such interaction. The structure of the bis-adduct was confirmed by single crystal X-ray diffraction. Actually, the formation of stable triethylammonium salts (as the process competitive with the 2-amino-4H-pyrans formation) appeared to be reversible and their interaction with active methylene nitriles led to the formation of 2-amino-4H-pyrans. The extended and adjusted mechanism of the three-component interaction, that includes the bis-adducts formation stage, was proposed. Taking into account the peculiarities of the mechanism, we were capable to control the reaction selectivity.

The regio- and stereoselective, catalyst-free multicomponent synthesis of spiro-conjugated dihydrofuran-2(3H)-one/triazolo[1,5-a]pyrimidine derivatives in good to high yields via a Biginelli approach starting from ortho-substituted benzaldehydes, 3-amino-1,2,4-triazole and α-acetylbutyrolactone is reported. A plausible reaction mechanism for this transformation is discussed. The obtained heterocycles possess a drug-like conformationally restricted structure with defined stereochemistry and increased stability compared to other products obtained by this mode of the Biginelli reaction.

(5 S ,7 R )-5-Aryl-7-methyl-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5- a ]pyrimidin-7-ols were synthesized by three-component reactions of 1 H- 1,2,4-triazol-3-amine with aromatic aldehydes and acetone in the presence of TsOH. Antimicrobial and antifungal activities of these new substances were investigated in vitro .

In the crystal, N—H⋯N hydrogen bonds link the mol­ecules into the supra­molecular chains propagating along the c-axis direction., The title compound, C19H19N5O2, was prepared by the reaction of 3-amino-5-(pyridin-3-yl)-1,2,4-triazole with acetone and 2-hy­droxy-3-eth­oxy­benzaldehyde. It crystallizes from ethanol in a tetra­gonal space group, with one mol­ecule in the asymmetric unit. The 1,2,4-triazole five-membered ring is planar (maximum deviation = 0.0028 Å). The pyridine and phenyl rings are also planar with maximum deviations of 0.0091 and 0.0094 Å, respectively. In the crystal, N—H⋯N hydrogen bonds link the mol­ecules into supra­molecular chains propagating along the c-axis direction. Hirshfeld surface analysis and two-dimensional fingerprint plots have been used to analyse the inter­molecular inter­actions present in the crystal.

Octahydroacridine-4-carbonitrile (carboxamide) was shown to react with aryldiazonium salts and other electrophilic reagents in acidic and neutral media. The reactions occurred at the methine carbon atom, forming the corresponding 4-functionalized derivatives. The obtained azo compounds decomposed at 140–155°С with elimination of nitrogen and gave products formed by the reactions of radical intermediates.

Derivatives of 7-amino-6-azaindole containing variable substituent in the amino group were synthesized via acid-catalyzed nucleophilic heteroaromatic substitution (SNHetarH+) using 7-chloro-6-azaindoles as substrates and aliphatic and aromatic amines as nucleophiles. The protonation of the pyridine nitrogen in the starting 7-chloro-6-azaindoles is presumed to be the key stage of the reaction mechanism discussed.

Modern methods for the synthesis of highly substituted 2-pyridones are overviewed making a special emphasis on the interaction between C1-electrophiles, α-carbonyl CH acids, and active methylene nitriles under microwave irradiation.

A reaction of 6-amino-1,3-dimethyluracil with 3-(hetero)aroylacrylic acids and their methyl esters leads to hexahydropyrido[2,3-d]pyrimidine-5-carboxylic acids or the corresponding methyl esters in high to excellent yields. One-pot oxidation of the acid derivatives with CAN is accompanied by decarboxylation to give tetrahydropyrido[2,3-d]pyrimidines, while oxidation with bromine resulted in the formation of tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acids. The aromatization of methyl hexahydropyrido[2,3-d]pyrimidine-5-carboxylates was achieved by K2CO3-mediated air oxidation under ambient conditions.

An efficient synthesis of 1-methyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine hydrochloride was achieved using simple sodium borohydride reduction of 6-benzyl-1-methyl-1H-pyrrolo[2,3-c]pyridin-6-ium bromide as the key step followed by its debenzylation with hydrogen over palladium on carbon on a multigram scale. Similarly, a series of N6-substituted 1-methyl-1H-pyrrolo[2,3-c]pyridin-6-ium halides were synthesized and reduced with sodium borohydride, showing this method to be applicable for the synthesis of different N6-substituted 1-methyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridines.

Background: Despite the substantial progress over the time, malaria remains a major public health concern and causing hundreds of thousands of deaths. Resistance to the available antimalarial therapy increases threat to the global public health. Objective: Overview of currently available antimalarials. Method: Literary survey. Results: The summarized data about different types of antimalarial therapies and their efficiency and modes of action. Conclusion: Despite the seemingly large number of the drugs currently available for malaria treatment, this arsenal is limited due to the narrow variation of their mechanism of action.

The new 2-amino-3-R-4-aryl-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine 5,5-dioxides were synthesized via three-component interaction of 1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with arylcarbaldehydes and active methylene nitriles. Depending on the nature of an active methylene nitrile and an arylcarbaldehyde this interaction can lead either to the target 2-amino-4H-pyrans or to the stable triethylammonium salts of bis(1H-2,1-benzothiazin-4(3H)-one 2,2-dioxides) (bis-adducts). The latter is a completely new product of such interaction. The structure of the bis-adduct was confirmed by single crystal X-ray diffraction. Actually, the formation of stable triethylammonium salts (as the process competitive with the 2-amino-4H-pyrans formation) appeared to be reversible and their interaction with active methylene nitriles led to the formation of 2-amino-4H-pyrans. The extended and adjusted mechanism of the three-component interaction, that includes the bis-adducts formation stage, was proposed. Taking into account the peculiarities of the mechanism, we were capable to control the reaction selectivity.

A facile method for the synthesis of substituted pyrrolo[2,3-c]pyridine-7-ones is developed that applies an acid-promoted intramolecular cyclization of 2-pyrrolecarboxylic acid amidoacetals as key step. The synthesis is easily scaled up to 1.5 mol quantity with no yield decrease. The alkylation/arylation reaction of the pyrrolo[2,3-c]pyridine-7-ones proceeds regioselectively giving N6-substituted derivatives.

New chiral derivatives of thiophene fused with menthane, camphor or the 3R-3-methylcyclohexane ring were prepared and studied as chiral dopants in cholesteric liquid crystalline mixtures. The helical twisting power of the most effective compounds of this series, menthothiophenes, was strong enough to obtain selective reflection of visible light at 16 wt% concentration of the dopant in a non-chiral nematic host.

Ethoxymethylenemalonodinitrile 1B and ethyl ethoxymethylenecyanoacetate 1C in cyclocondensations with 2-cyanoacetanilides 2 behave as a three-carbon fragment transfer reagent to afford the corresponding 5-cyano- and 5-ethoxycarbonyl-6-amino-1-aryl-3cyanopyridin-2(1H)-one derivatives 7B and 8C. One carbon transfer described earlier for such reactions with a use of diethyl 2-(ethoxymethylene)malonate 1A was observed only as a side process in the case of 1C leading to 2-amino-5-cyano-6-oxo-N,1-diaryl-1,6-dihydropyridine-3carboxamides.

A novel one-pot three-step method for the synthesis of 2,5-dioxo-5,6,7,8-tetrahydro-2H-chromene-3-carboxamide derivatives via hydrolysis of 4-cyanobuta-1,3-dienolate salts was developed. These chromenes contain a 2-pyrone scaffold which is present in many well-known natural and synthetic biologically active compounds. Employing our protocol, a 55 compounds library was quickly generated from 1,3-cyclohexanediones, dimethylformamide dimethylacetal, and various N-substituted cyanacetamides.

A vacuum microwave-assisted dehydration process of orthophosphoric acid for preparation of polyphosphoric acid was studied in comparison with the conventional dehydration in terms of energy efficiency and process rates. The influence of the applied microwave-power input on the process duration and the efficiency of microwave process were examined. The optimal microwave power input provided twofold shortening of the process time compared to conventional heating. At the same time the energy efficiencies remained comparable for both heating modes which was caused by nonoptimal filling ratio of the microwave cavity. The perspectives of the process scale-up in terms of increasing energy efficiency were also discussed.

The effect of the intramolecular H-bonding of the primary amide group on the spectral properties and reactivity of this group towards electrophiles has been studied in systematic rows of 1,2,5,6,7,8-hexahydro-7,7-dimethyl-2,5-dioxo-1-R-quinoline-3-carboxamides and 2-aryliminocoumarin-3-carboxamides using 1H and 15N NMR spectroscopy and the kinetics of model reactions. The upfield signal of the amide proton that is not intramolecularly H-bonded (Ha) depends on external factors such as solvent nature and concentration. At the same time, the downfield chemical shift of the Hb proton (bonded by the intramolecular hydrogen bond) depends mostly on the strength of the intramolecular H-bond, which is affected by such internal factor as electron nature of substituent R. The substituent's influence on the Hb proton's chemical shift is more effective in deuterochloroform medium than in DMSO-d6 where the intramolecular hydrogen bond is less stable. The value Δδ(H) = δ(Hb) − δ(Ha) is suggested as a simple comparative spectral index of the intramolecular hydrogen bond strength in these and similar compounds. By contrast, the effect of R on the 15N NMR chemical shift of the amide nitrogen has turned out to be too small to estimate changes of the electron density at the nitrogen. The effect of the intramolecular H-bond on the reactivity of the amide group is twofold. When the cleavage of the H-bond occurs on the rate limiting step it dramatically reduces the reaction rate. In the other case, the strengthening of the H-bond favors the reaction rate because of the increase of the electron density at the amide nitrogen. Copyright © 2011 John Wiley & Sons, Ltd.

A sodium ethoxide catalyzed reaction of N-substituted cyanoacetanilides 1a-f with diethyl 2-(ethoxymethylene)malonate 2 unexpectedly leads to the corresponding 2-amino-5-cyano-6oxo-N,1-diaryl-1,6-dihydropyridine-3-carboxamides 3a-f, while the expected 5-cyano-2hydroxy-6-oxo-1-aryl-1,6-dihydropyridine-3-carboxylates 4a-f were observed only as minor products.

A Biginelli-like three-component condensation using 3-amino-1,2,4-triazole as urea component resulted in an unexpected alternative direction of the tetrahydropyrimidine ring formation.

Representative benzimidazopyrimidinones were previously reported to be intercalating antitumor agents. In this work, we used 2-substituted 4,10-dihydrobenzo Dihydrobenzo[4,5]imidazo[1,2-a]pyriminin-4-ones for their diversification by regioselective alkylation. Under the conditions established, the alkylation gave 10-alkyl derivatives which permitted the parallel generation of a 500-member library of the title compounds.

Dimethylamino)but-3-en-2-one 1a reacted with malononitrile 2a affording (2E,4E)-2-cyano- 5-dimethylamino)hexa-2,4-dienamide 6aa that was isolated as two isomers,1-s-cis and 1-s-trans 6aa as confirmed by X-ray diffraction analysis. Acid-induced cyclization of 1-s-cis 6aa gave the known 1,2-dihydro-6-methyl-2-oxopyridine-3-carbonitrile 3aa, but not 1,2-dihydro-4-methyl-2- oxopyridine-3-carbonitrile 9aa as reported previously. The mechanistic pathway of the 2- pyridone ring formation is discussed.

The 2-aryl-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-ones and 2-aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-ones have been diversified by alkylation reactions, applying benzylchlorides and N-substituted 2-chloroacetamides as alkylating agents. Under the found uniform conditions the substitution direction does not depend on the structure of the alkylating agent and gives monoalkylated products in high yields with simple workup. The alkylation of the 2,3-dihydropyrimidin-4(1H)-one derivatives proceeds onto the N1-position; however, in the case of pyrimidin-4(3H)-ones the O-alkylated products are formed selectively. An alternative strategy for the synthesis of the N1-benzyl-2,3-dihydropyrimidin-4(1H)-one derivatives is also developed. It applies the redaction of N2-substituted Gewald's amides with aromatic aldehydes and allows simple introduction of various substituents in the final molecule.

A general review (138 references) focused on the recent advances in the application of Meldrum's acid reactivity for synthesis of diverse pyridine and pyrimidine derivatives, mostly small and drug-like molecules is presented.

Various 2-(2-cyano-2-carbamoyl-1-ethenyl)-5,5-dimethyl-3-oxo-1-cyclohexen-1-olates substituted in the amide group with dialkylammonium or sodium cations were prepared via reactions of N-substituted cyanoacetamides with dimedone–DMFDMA adduct by a one-pot, two-step protocol. The salts obtained were used in reactions with N-nucleophiles for further synthesis of the N1-substituted 2,5-dioxo-1,2,5,6,7,8-hexahydro-3-quinolinecarboxamides that are analogues of well-known pharmaceuticals. The structure of the salts and the N1-substituted 2,5-dioxo-1,2,5,6,7,8-hexahydro-3-quinolinecarboxamides was established by means of spectroscopic and X-ray diffraction studies.

Transformations of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (Gewald's amide) in the reactions with aromatic aldehydes were studied. Efficient methods for synthesis of three possible types of products: 2-aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one, 2-(1-arylmethylidene-amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide and 2-aryl-2,3,5,6,7,8-hexahydro[1]benzo-thieno[2,3-d]pyrimidin-4(1H)-one derivatives were developed. All the products were easily isolated by filtration in very good overall yields. Mutual transformations of these compounds were also studied.

Derivatives of 7-amino-6-azaindole containing variable substituent in the amino group were synthesized via acid-catalyzed nucleophilic heteroaromatic substitution (SNHetarH+) using 7-chloro-6-azaindoles as substrates and aliphatic and aromatic amines as nucleophiles. The protonation of the pyridine nitrogen in the starting 7-chloro-6-azaindoles is presumed to be the key stage of the reaction mechanism discussed.

Among the diversity of natural and synthetic compounds being studied and applied for human welfare, peptides able to develop nanostructures are currently under special attention of scientists. In this review, we focus on such properties of peptides and various kinds of intramolecular interactions allowing their ability to form different shapes of nanoassemblies. We have also discussed the applications of self-assembled peptides in various biomedical fields where they can be employed as cargo to target delivery of drugs, genes, in tissue engineering, regenerative medicines, and biosensors.

2-Pyridone and 2-quinolone analogues are well-known biologically active heterocyclic scaffolds. Libraries of 3,5,6-substituted 2-pyridone derivatives are generated by rapid microwave assisted solution phase methods using a one-pot, two-step protocol. The three-component condensation of CH–acidic carbonyl compounds, N,N-dimethylformamide dimethylacetal and methylene active nitriles, leads to 2-pyridones and fused analogues in moderate to good overall yields and high purities. The proposed mechanism of this novel multi-component reaction, structure elucidation of products and intermediates are discussed.

[reaction: see text] The solution-phase synthesis of N3-acylated dihydropyrimidines was achieved utilizing microwave flash heating both in the synthesis (acylation) and purification (scavenging) steps. Quenching times for excess anhydrides using polystyrene or silica-supported diamine sequestration reagents were reduced from several hours to minutes utilizing microwave irradiation. The use of water as sequestration agent, coupled with an efficient solid-phase extraction workup technique allowed the rapid generation of a 20-member library of N3-acylated dihydropyrimidines.