Search

Background: In this study, two novel hybrid series of artemisinin and quinazolinones were synthesized and evaluated in vitro cytotoxicity against two human cancer cell lines, including SKLu-1 (lung cancer), MCF- 7 (breast cancer). The bio-assay results indicated that most of the target compounds exhibited cytotoxic activities against both human cancer cell lines tested and seemed to be more cytotoxic toward the breast (MCF-7) cancer cells than lung (SKLu-1) cancer cells. Among the synthesized artemisinin hybrids, the compound 13d containing a quinazolinone conjugated system exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 μM, respectively. Objective: This study aims at developing novel hybrids of artemisinin and quinazolinones as anticancer agents. Method: A series of novel hybrids were designed, synthesized, and evaluated for cytotoxicity against two human cancer cell lines, including SKLu-1 and MCF-7, using the SRB method. Results: All thirteen hybrids of artemisinin with quinazolinone exhibited cytotoxic activity against two tested cancer cell lines, in which the compound 13d exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 μM, respectively. Conclusion: The research results suggest that some compounds could be considered as leads for future design of hybrids and have the potential for further studies in the field of anti-cancer agent development.

Twenty 1,4-pentadiene-3-one derivatives containing quinazolinone (W1–W20) were designed and synthesized. The bioactivity test results showed that some compounds had antifungal activities in vitro. W12 showed excellent bioactivity against Sclerotinia sclerotiorum (S. sclerotiorum) and Phomopsis sp., with EC50 values of 0.70 and 3.84 μg/mL, which are higher than those of the control drug azoxystrobin at 8.15 and 17.25 μg/mL. In vivo activity tests were carried out on oilseed rape and kiwifruit. The protective effect of W12 on oilseed rape infected with S. sclerotiorum (91.7 and 87.3%) was better than that of azoxystrobin (90.2 and 79.8%) at 100 and 50 μg/mL, respectively, and the protective effect on kiwifruit infected with Phomopsis sp. (96.2%) was better than that of azoxystrobin (94.6%) at 200 μg/mL. Scanning electron microscopy results showed the hyphae of S. sclerotiorum treated with compound W12 abnormally collapsed and shriveled, inhibiting the growth of mycelium and, thus, laying the inhibiting effect on S. sclerotiorum. The results of the mechanism research showed that the action of W12 changed the mycelial morphology of S. sclerotiorum, affected the permeability of cells, increased the leakage of cytoplasm and allowed the cell membrane to break down. This study shows that 1,4-pentadiene-3-one derivatives containing quinazolinone have good effects on plant fungi and the potential for becoming new fungicides.

In the report, we described the ruthenium(II)-catalyzed C–H activation/cyclization of 2-arylquinazolinones with vinyl carbonate for the synthesis of different fused quinazolinones. Through this strategy, the 6-hydroxy-5,6-dihydro-8H-isoquinolino[1,2-b]quinazolin-8-one and 8H-isoquino[1,2-b] quinazolin-8-one have been obtained, respectively, under different temperatures. Additionally, the reaction features broad substrate scope and good yields, only producing carbon dioxide as byproduct. Moreover, we performed preliminary mechanistic studies of this reaction and proposed a possible mechanism.

An expedient route to enantiopure, diastereomeric pyrrolopyrazinoquinazolinones was developed following the discovery of a domino quinazolinone rearrangement-intramolecular cyclization of N-H benzamidines. A Ugi-Mumm-Staudinger sequence employing an optically pure proline derivative gave quinazolinones that, upon N-Boc deprotection, rearranged to tautomeric Z-benzamidines. Subsequent spontaneous cyclization afforded 15 diastereomeric pyrazinoquinazolinone pairs in up to 83% overall yield and 89:11 d.r which were separated easily via routine chromatographic purification – the only one required in the entire process.

For the first time, the sequential reaction of peroxyoxindole that involves base-promoted oxidative fragmentation to isocyanate formation and primary amine or amino alcohol accelerated skeletal rearrangement to synthesize exo-olefinic-substituted quinazolinone or oxazoloquinazolinone is reported. The advantages of this new reaction include a broad substrate scope and transition-metal-free and room-temperature conditions. The formation of the isocyanate as a key intermediate that accelerates oxidative skeletal rearrangement has been confirmed by trapping experiments and spectroscopic evidence.

Chikungunya virus (CHIKV) has repeatedly spread via the bite of an infected mosquito and affected more than 100 countries. The disease poses threats to public health and the economy in the infected locations. Many efforts have been devoted to identifying compounds that could inhibit CHIKV. Unfortunately, successful clinical candidates have not been found yet. Computations through the simulating recognition process were performed on complexation of the nsP3 protein of CHIKV with the structures of triply conjugated drug lead candidates. The outcomes provided the aid on rational design of functionalized quinazoline-(α-substituted coumarin)-arylsulfonate compounds to inhibit CHIKV in Vero cells. The molecular docking studies showed a void space around the β carbon atom of coumarin when a substituent was attached at the α position. The formed vacancy offered a good chance for a Michael addition to take place owing to steric and electronic effects. The best conjugate containing a quinazolinone moiety exhibited potency with EC50 = 6.46 μM, low toxicity with CC50 = 59.7 μM, and the selective index (SI) = 9.24. Furthermore, the corresponding 4-anilinoquinazoline derivative improved the anti-CHIKV potency to EC50 = 3.84 μM, CC50 = 72.3 μM, and SI = 18.8. The conjugate with 4-anilinoquinazoline exhibited stronger binding affinity towards the macro domain than that with quinazolinone via hydrophobic and hydrogen bond interactions. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:23 issue:14 ispartof: location:Switzerland status: published

A series of new quinazolinones and related compounds has been conveniently synthesized via reaction of (E)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(6-iodo-4-oxo-4H-benzo[d] [1,3] oxazin-2-yl)acrylonitri...

Electrochemistry has recently emerged as a sustainable approach for efficiently generating radical intermediates utilizing eco-friendly electric energy. An electrochemical process was developed to transform 1,2,4-oxadiazolines under mild conditions. The electrochemical N-O bond cleavage at a controlled oxidation potential led to the selective synthesis of quinazolinone derivatives that could not be obtained by photocatalytic radical processes, indicating complementary reactivities in radical processes. The electrochemical reaction pathways were fully revealed by density functional theory-based investigations.

A visible-light-initiated cross-dehydrogenative-coupling amination is described, featuring metal- and photocatalyst-free, at room temperature, and using air as an oxidant. The reaction provides a facile approach for the synthesis of rutaecarpine and its derivatives. The substrates with electron-withdrawing groups give higher yields than those with electron-donating groups, but the substituent position has a negligible influence on the yield. Using binaphthyl-diyl hydrogen phosphate and dibenzyl phosphate as catalysts both deliver satisfying yields. This straightforward light-driven strategy might be applicable to the synthesis of quinazolinone derivatives.

A variety of dihydroquinazolin-4(1H)-one derivatives (1–37) were synthesized via “one-pot” three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02—88.65 ± 0.23 μM) and α-glucosidase (IC50 = 25.01 ± 0.12—89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 μM for α-amylase and IC50 = 17.67 ± 0.09 μM for α-glucosidase). Structure–activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.

A family of axially chiral quinazolinone-based heterobiaryls were constructed with high levels of enantiocontrol (up to 94% ee). Convergently, three different synthetic methods have been realized to prepare these valuable compounds including central-to-axial chirality transfer, dynamic kinetic resolution, and phase-transfer catalysis. Importantly, novel P,N-ligands with a π-π stacking can be derived from heterobiaryls by chirality exchange strategy or synthesized directly from complementary phase-transfer catalysis by using the inexpensive chiral quaternary ammonium salt.

3-(Naphthalen-1-yl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one 1, and its S-alkylated products 2–6, were effectively synthesized under ultrasonic irradiation under greener reaction condition with low...

Five new tyrosine derivatives (1-5), one new phenylacetic acid derivative (6), two new quinazolinone analogues (7 and 8), one new naphthalenedicarboxylic acid (9), and one new 3,4-dihydroisocoumarin derivative (10), together with seven known compounds, were isolated from the fungus Xylaria sp. FM1005, which was isolated from Sinularia densa (leather coral) collected in the offshore region of the Big Island, Hawaii. The structures of compounds 1-10 were elucidated by extensive analysis of NMR spectroscopy, HRESIMS, and ECD data. Due to their structure similarity to the antiplatelet drug tirofiban, compounds 1-5 together with 6 were investigated for their antithrombotic activities. Compounds 1 and 2 strongly inhibited the binding of fibrinogen to purified integrin IIIb/IIa in a dose-dependent manner with the IC50 values of 0.89 and 0.61 μM, respectively, and compounds 1 and 2 did not show any cytotoxicity against A2780 and HEK 293 at 40 μM.

In this study, a new series of quinazolinone-1,2,3-triazole-acetamide hybrids 8a–m, using by molecular hybridization of the potent α-glucosidase inhibitor pharmacophores, was designed and evaluated against carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase. All the synthesized compounds with IC50 values in the range of 45.3 ± 1.4 µM to 195.5 ± 4.7 µM were significantly more potent than standard inhibitor against α-glucosidase, while these compounds were not active against α-amylase in comparison to standard inhibitor. Representatively, compound 8a with IC50 = 45.3 ± 1.4 µM was around 17 times more potent than standard inhibitor acarbose (IC50 = 750.0 ± 12.5 µM). The inhibition kinetic analysis of the compound 8a indicated that this compound was a competitive α-glucosidase inhibitor. Molecular modeling analysis confirmed that the most potent inhibitors 8a and 8b well accommodated in the modeled α-glucosidase active site and it was also revealed that these compounds formed stable inhibitor–receptor complexes with the α-glucosidase in comparison to acarbose. In silico pharmacokinetic and toxicity of the most potent compounds were evaluated and obtained results were compared with acarbose. Furthermore, the most potent compounds were also evaluated against human normal cells and no cytotoxicity was observed.

Simple ammonium ionic liquids [ILs] are efficient, green, environmentally friendly catalysts in promoting the Biginelli condensation reaction, Hantzsch reaction and Niementowski reaction to afford 1,2,3,4-tetrahydropyrimidine, 2-aminothiazole and quinazolinone derivatives respectively by eliminating the need for harmful volatile organic solvents. These [ILs] are air and water stable, easy to prepare and cost-effective. The effects of the anions and cations present in [IL] on reactions were investigated. The results clearly indicated that the Biginelli condensation reaction, Hantzsch reaction and Niementowski reaction were heavily influenced by the acidity of [IL], and among various ammonium ionic liquids, [Et3NH][HSO4] showed the best catalytic activity. Furthermore, [IL] could be easily separated and reused with a slight loss of its activity. This technique provided a good alternative way for the industrial synthesis of 1,2,3,4-tetrahydropyrimidinones, 2-aminothiazoles and quinazolinones. The present processes are eco-friendly methods for the synthesis of these derivatives authenticated by several green parameters, namely, E-factor, process mass intensity, reaction mass efficiency, atom economy, and carbon efficiency.

This is the first report on a facile tandem route for synthesizing quinazolinones at room temperature from various aminobenzamides and in situ-generated aldehydes. The latter was formed via CC bond cleavage, and the overall reaction proceeded using molecular oxygen as a clean oxidant in the absence of a photocatalyst. Visible light, which was indispensable for the entire course of the reaction, played multiple roles. It initially cleaved styrene to an aldehyde, then facilitated its cyclization with an o-substituted aniline, and finally promoted the dehydrogenation of the cyclized intermediate. The previous step provided the feedstock for the next step in the reaction, thereby preventing volatilization, oxidation, and polymerization of the aldehyde. Thus, the overall process is simple, environmentally benign, and economically feasible.

Glycosylated natural products and their derivatives are important pharmaceutical agents. Genome mining of a C-glycosylated metabolite biosynthetic gene cluster (BGC) from a soil-derived Streptomyces strain led to the isolation of sarubicins A (1) and B (2), of which 1 has a rare 2-oxabicyclo[2.2.2] substructure arising from C-glycosylation and C–C bond formation between the aglycone and the C-4 position of deoxysugar. Heterologous expression of the sar BGC led to the production of sarubicins and three new C-glycosylated quinazolinones 3–5 with a single C–C bond between the aglycone and deoxysugar, indicating the stepwise formation mechanism of the two unusual C–C bonds. A convenient chemical transformation from 1 to 2 and a proposed biosynthetic pathway for sarubicins are presented. Significantly, compounds 1 and 2 showed potent protective effects on neonatal rat cardiomyocytes.

Heterocycle-fused quinazolinone derivatives have attracted great attention due to their diversified biological and optical activities. In this study, a novel one-pot palladium-catalyzed cascade C–C coupling/cyclization/aromatization of 2-(4-oxoquinazolin-3(4H)-yl)acetonitrile derivatives with arylboronic acids has been disclosed to synthesize 1,3-diaryl-6H-pyrazino[2,1-b]quinazolin-6-one in water. This protocol provides an efficient access to valuable pyrazino-fused quinazolinones in a green solvent (i.e., water) with yields ranging from moderate to excellent. Furthermore, the photophysical properties of these molecules were investigated. The resultant pyrazino-fused quinazolinones exhibit tunable fluorescence, and 3e displays the aggregation induced emission properties with a large Stokes shift. This study provides a useful approach to the development of pyrazino-fused quinazolinones, which have potential applications in chemistry, biology, and materials science.

The quinazolinone skeleton is a common structure found in natural alkaloids and synthetic drugs. In recent years, some quinazolinone derivatives have been found to exhibit good luminescence properties. Benefitting from excellent biocompatibility, low toxicity, and high efficiency, quinazolinones have become promising candidates for use as fluorescent probes, biological imaging reagents and luminescent materials. This review focuses on recent advances relating to the luminescence properties of quinazolinones and their applications in fluorescent probes, biological imaging. Fluorescent probes based on the 2-(2′-hydroxyphenyl)-4(3H)-quinazolinone (HPQ) structure are summarized. Newly developed quinazolinone molecules for environmentally sensitive probes and two photon fluorescence bioimaging are discussed. A brief outlook relating to the future of quinazolinone-based probes and luminescent materials is also included.

An efficient protocol for obtaining fused quinazolinones through an oxidative free-radical cyclization under metal- and tin-free conditions is described. The oxidative cyclization of various N-3-ω-iodoalkyl derivatives to provide tricyclic systems using dicumyl peroxide as the sole reagent is studied. The method then is employed for the syntheses of 5-, 6-, and 7-membered fused quinazolinone analogues, including the natural products deoxyvasicinone and mackinazolinone. A xanthate-based oxidative radical cascade addition/cyclization process that allows the production of new menthol- and testosterone-quinazolinone conjugates, as well as the first total synthesis of leucomidine C, are also reported.

A novel and efficient procedure for the generation of quinazolinone phosphonate derivatives employing the reaction of euparin, isatin or its derivatives, primary amines, dialkyl acetylenedicarboxylates, trimethyl phosphite or triphenyl phosphite, and acidic solution of hydrogen peroxide in aqueous media at ambient temperature under ultrasonic irradiation was developed. Without ultrasonic irradiation, the reaction does not proceed and agitation of the reaction mixture is difficult. Some advantages of this procedure are: short time of reaction, high yields of products, easy isolation of products.

Background: Imidazo[1,2-a]pyrimidinone, quinazolinone and amide derivatives have attracted a lot of interest because of their broad scope of biological and pharmacological activities. There are a lot of methods reported in the literature for their synthesis. Therefore, we became interested in developing a convenient synthetic method for the preparation of imidazoquinazolinone and amide derivatives. Objective: NiFe2O4@SiO2 @glucose amine were synthesized, characterized and have been used for the green, effective and mild multicomponent synthesis of quinazolinones, benzoimidazo[1,2-a]pyrimidinones and amides under solvent-free conditions in short reaction times and excellent yields. To expand of the scope of this avenue, multicomponent synthesis of mono and bis novel amides was tested for the first time. All of the products were characterized by mp, FT-IR, NMR and elemental analysis. Methods: Aldehyde (1mmol), 2-amino benzimidazole (1 mmol), dimedone (1mmol) or indane-1,3-dione (1 mmol) for the synthesis of quinazoline or imidazopyrimidinones and arene (1mmol), anhydride (1mmol), 2- aminobenzimidazole (1mmol) for the synthesis of amides in the nanocatalyst NiFe2O4@SiO2@glucose amine (0.15mol%: 0.05g) were stirred by a magnet for the required reaction time. After completion of the reaction, as indicated by TLC, the products were collected and recrystallized from ethanol if necessary. Results: We present a novel avenue for the synthesis of benzimidazo[1,2-a] pyrimidinones, quinazolinones and amides in the presence of NiFe2O4@SiO2@glucose amine under solvent-free conditions. Conclusion: In conclusion, we developed NiFe2O4@SiO2 @glucose amine-catalysed multicomponent synthesis of quinazolinones and imidazo[1,2-a]pyrimidinones using the reaction of benzaldehyde, dimedone or indane-dione and 2-aminobenzimidazole and multicomponent synthesis of amides using arenes, cyclic anhydrides and 2-aminobenzimidazole by a solvent-free technique. This method proves to be a robust and innovative approach for the synthesis of a biologically important structure. The operational simplicity, the excellent yields of products, ease of separation and recyclability of the magnetic catalyst, waste reduction and high selectivity are the main advantages of this method. Furthermore, this new avenue is cheap and environmentally benign.

Aim With the rapid emergence of antibiotic resistance, efforts are being made to obtain new selective antimicrobial agents. Hybridization between quinazolinone and benzenesulfonamide can provide new antimicrobial candidates. Also, the use of nanoparticles can help boost drug efficacy and lower side effects. Materials and methods Novel quinazolinone-benzenesulfonamide derivatives 5-18 were synthesized and screened for their antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, MRSA and yeast. The most potent compound 16 was conjugated with copper oxide nanoparticles 16-CuONPs by gamma irradiation (4.5 KGy). Characterization was performed using UV-Visible, TEM examination, XRD patterns and DLS. Moreover, compound 16 was used to synthesize two nanoformulations : 16-CNPs by loading 16 in chitosan nanoparticles and the nanocomposites 16-CuONPs-CNPs. Characterization of these nanoformulations was performed using TEM and zeta potential. Besides, the inhibitory profile against Staphylococcus aureus DNA gyrase was assayed. Cytotoxic evaluation of 16, 16-CNPs and 16-CuONPs-CNPs on normal VERO cell line was carried out to determine its relative safety. Molecular docking of 16 was performed inside the active site of S. aureus DNA gyrase. Results Compound 16 was the most active in this series against all the tested strains and showed inhibition zones and MICs in the ranges of 25-36 mm and 0.31-5.0 µg/mL, respectively. The antimicrobial screening of the synthesized nanoformulations revealed that 16-CuONPs-CNPs displayed the most potent activity. The MBCs of 16 and the nanoformulations were measured and proved their bactericidal mode of action. The inhibitory profile against S. aureus DNA gyrase showed IC50 ranging from 10.57 to 27.32 µM. Cytotoxic evaluation of 16, 16-CNPs and 16-CuONPs-CNPs against normal VERO cell lines proved its relative safety (IC50= 927, 543 and 637 µg/mL, respectively). Molecular docking of 16 inside the active site of S. aureus DNA gyrase showed that it binds in the same manner as that of the co-crystallized ligand, ciprofloxacin. Conclusion Compound 16 could be considered as a new antimicrobial lead candidate with enhanced activity upon nanoformulation.

Supporting information for this article is given via a link at the end of the document. By intercepting the acylpalladium species with C=N bond of azaarenes or imines other than free amines or alcohols, the difunctionalization of C=N bond was established via palladium-catalyzed carbonylation/nucleophilic addition sequence. This method is compatible with a diverse range of azaarenes and imines and allows for the efficient synthesis of a wide range of quinazolinones and derivatives. The synthetic utility has been demonstrated by one-step synthesis of evodiamine and its analogue with inexpensive starting materials.

A convenient oxidative cyclodesulfurization method toward the synthesis of benzofused nitrogen heterocycles using inexpensive and readily available potassium periodate as an oxidant was developed. Upon treating isothiocyanates with ortho-substituted anilines bearing N,N-, N,O-, and N,S-bis-nucleophiles, followed by an intramolecular cyclization of the in situ generated monothioureas, substituted 2-aminobenzazole series were rapidly accessible in good to excellent yields. The protocol can accommodate various substituents on both substrates while allowing more efficient, greener, and operational simpler process relative to other oxidative coupling reactions. Tetracyclic quinazolinone derivatives were also afforded in high yields in a single preparative step and chromatography-free.

In this research, the synthesis of the quinazolinone derivatives by the reaction of diaminoglyoxime with anthranilic acid or methyl 2-amino benzoate over an acetic acid-functionalized magnetic silica-based catalyst in water was described. The acetic acid-functionalized catalyst was prepared using a three-step procedure from magnetite NPs that initially coated with a layer of silica through the sol-gel process, modified with an aminosilane layer and functionalized with bromoacetic acid. The catalyst was characterized by means of spectroscopic and microscopic techniques, and its activity was investigated for the synthesis of the quinazolinones, bisquinazolinone and oxadiazole quinazolinones obtained from diaminoglyoxime in water at room temperature.

A radical domino cyclisation reaction of N-cyanamide alkenes, mediated by hydrogen atom transfer (HAT) has been developed. This method, using PhSiH3 and catalytic Fe(acac)3 , allows for the synthesis of challenging (spiro)quinazolinone scaffolds from simple, tractable (hetero)aryl carboxylic acid and cyanamide building blocks.

The use of the in situ generated ligand–copper superoxo complex absorbing light energy to activate the alpha C(sp3)–H of MeOH and EtOH via the hydrogen atom transfer (HAT) process for the synthesis of quinazolinones by oxidative cyclization of alcohols with o-aminobenzamide has been investigated. The synthetic utility of this protocol offers an efficient synthesis of a quinazolinone intermediate for erlotinb (anti-cancer agent) and 30 examples were reported.

We report a silver-catalyzed hydroalkoxylation of C2-alkynyl quinazolinones to prepare a series of novel quinazolinone-fused eight-membered N,O-heterocycles in good-to-excellent yields through a selective 8-endo-dig cyclization. Mechanistic studies revealed that the silver catalyst might aid bidentate coordination of an imine group and alkyne to facilitate 8-endo-dig cyclization to afford eight-membered N,O-heterocycles. Also, the proposed bimetal silver intermediates might promote hydroalkoxylation rapidly for quinazolinones bearing terminal alkynes at the C2-position. Biological evaluations revealed that most of the designed quinazolinone-fused eight-membered N,O-heterocycles inhibited nitric-oxide generation significantly in lipopolysaccharide-stimulated RAW264.7 cells and displayed their bioactivity as potentially good anti-inflammatory agents.

Quinazolinone and its congeners are ubiquitous structural motifs found in numerous natural products due to their wide applications as anticancer, antiviral, anti-inflammatory, antifolate and antitumor agents etc. Previously, the synthetic community devoted their efforts towards synthetic approaches but recent years have also witnessed an upsurge in the diversification of this scaffold and its applications. Thus, this review (from 2011 to the beginning of 2020) comprehensively focuses on transition metal catalyzed C-H bond functionalization namely arylation, amination, acetoxylation, amidation, alkylation, alkenylation, alkynylation, halogenation, thiolation, trifluoroethylation etc. of quinazolin-4(3H)-one. Additionally, we also briefly elucidate the plausible mechanistic pathways, scope and limitations.

An efficient, metal free and environment friendly synthesis of isoquinoline-fused benzimidazole has been developed via in situ air oxidation. Also, syntheses of isoquinoline-fused quinazolinone heteroacenes were successfully achieved. The synthesized isoquinoline-fused benzimidazole and isoquinoline-fused quinazolinone derivatives showed λmax, Fmax and Φf values in the ranges 356-394 nm, 403-444 nm and 0.063-0.471, respectively, in CHCl3.

N-heterocyclic compounds, such as quinazolinone derivatives, have significant biological activities. Nowadays, as the demand for environmentally benign, sustainable processes increases, the application of compounds from renewable sources, easily separable heterogeneous catalysts and efficient, alternative activation methods is of great importance. In this study, we have developed a convenient, green procedure for the preparation of 3a-methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazoline-1,5-dione through a double cyclocondensation cascade using anthranilamide and ethyl levulinate. Screening of various heterogeneous Brønsted acid catalysts showed that Amberlyst® 15 is a convenient choice. By applying mechanochemical activation in the preparation of this N-heterotricyclic compound for the first time, it was possible to shorten the necessary time to three hours compared to the 24 h needed under conventional conditions to obtain a high yield of the target product.

A green synthetic procedure was developed for the two-step synthesis of methyl 2-((3-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)thio)acetate from anthranilic acid, using two green chemistry approaches: utilization of the DES and microwave-induced synthesis. The first step includes a synthesis of 2-mercapto-3-(3-methoxyphenyl)quinazolin-4(3H)-one which was performed in choline chloride:urea DES. In the second step S-alkylation of 2-mercapto-3-(3-methoxyphenyl)quinazolin-4(3H)-one was performed in a microwave-induced reaction. The desired compound was successfully obtained in a yield of 59% and was characterized by different spectral methods.