Synthesis Of Quinazolinone Derivatives Research Articles

Green Synthetic and Pharmacological Developments in the Hybrid Quinazolinone Moiety: An Updated Review.

Bicyclic quinazolinone constitutes an important class of organic framework enveloping numerous biological properties which enthused organic and medicinal chemists to explore green synthetic strategies for the construction of quinazolinone hybrids with significantly improved pharmacodynamics and pharmacokinetic profiles. In this perspective, the present review summarizes the most recent green synthetic strategies, biological properties, structure-activity relationship, and molecular docking studies of the 4-quinazolinone-based scaffold. This review provides deeper insight into the hit-to-lead synthesis of quinazolinone derivatives in the development of clinically important therapeutic candidates.

Synthesis of quinazolinone derivatives with a seven‐membered ring using borrowing hydrogen methodology

In this study, we synthesized 23 quinazolinone derivatives with the seven-membered C-ring through intramolecular borrowing hydrogen reaction of 3-(3-hydroxypropyl)-2-(1H-indol-2-yl)-quinazolin-4(3H)-one, in yields ranging from 31 % to 68 %. The reaction took place in the presence of cesium carbonate and DMF, using triphenylphosphine ruthenium chloride (PPh3)3RuCl2 as a catalyst and Xantphos as a ligand. Water was the only byproduct. Furthermore, pharmacological activity tests were conducted on these compounds, revealing that some of the products exhibited anti-inflammatory and anticancer properties.

Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 μg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.

Environmentally Friendly Approach to the Synthesis of 3-[Benzylideneamino]-2-methylquinazolin-4(3H)-one Derivatives and Calculation of Their Toxicity.

Application of deep eutectic solvents in synthesis of different heterocyclic compounds was proven very efficient. These solvents are a new generation of green solvents showing excellent potential for different purposes, where they are used as environmentally acceptable substitute for toxic and volatile organic solvents. This research describes their application in the synthesis of series of quinazolinone Schiff bases in combination with microwave, ultrasound-assisted and mechanochemical methods. First, a model reaction was performed in 20 different deep eutectic solvents to find the best solvent and then reaction conditions (solvent, temperature and reaction time) were optimized for each method. Afterwards, 40 different quinazolinone derivatives were synthesized in choline chloride/malonic acid (1 : 1) DES by each method and compared by their yields. Here we show that deep eutectic solvents can be very efficient in the synthesis of quinazolinone derivatives as an excellent substitution for volatile organic solvents. With green chemistry approach in mind, we have also performed a calculation on compounds' toxicity and solubility, showing that most of them possess toxic and mutagenic properties with low water solubility.

Synthesis of quinazolinone derivatives containing an acyl hydrazone skeleton as potent anti-urease agents enzyme kinetic studies and anti-oxidant properties

This paper covers the synthesis, in vitro urease inhibition, enzyme kinetic parameters, and anti-oxidant studies of a novel series of quinazolinone derivatives containing an acyl hydrazone skeleton. Compounds 3a, 3b, 5a, and 5b, having IC50 values ranging from 1.86 ± 0.07 to 6.38 ± 0.11 µg mL−1, show greater inhibitory activity than the standard inhibitor, thiourea. Among the products, (2-[2-(3-methoxybenzyl)-4-oxoquinazolin-3(4 H)-yl]acetohydrazide) proves to be the most potent, exhibiting enzyme inhibition activity with an IC50 value of 1.86 ± 0.07 µg mL−1. Kinetic studies involving the Lineweaver–Burk plots reveal that the inhibition mechanism of the most active compounds (3a, 3b, 5a, and 5b) on urease activity are found to be in competitive mode. Also, the anti-oxidant activity and radical-scavenging properties of the synthesized compounds are evaluated using cupric reducing anti-oxidant activity, ferric reducing anti-oxidant capacity, 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), and 2,2-diphenyl-1-picrylhydrazyl assays. Compounds 3a, b and 5a, b have good anti-oxidant properties and radical-scavenging activity at various final concentrations.

Transition-metal-free radical difluorobenzylation/cyclization of unactivated alkenes: access to ArCF2-substituted ring-fused quinazolinones.

A mild and efficient transition-metal-free radical difluorobenzylation/cyclization of unactivated alkenes toward the synthesis of difluorobenzylated polycyclic quinazolinone derivatives with easily accessible α,α-difluoroarylacetic acids has been developed. This transformation has the advantages of wide functional group compatibility, a broad substrate scope, and operational simplicity. This methodology provided a highly attractive access to pharmaceutically valuable ArCF2-containing polycyclic quinazolinones.

Scaffold hopping and optimisation of 3’,4’-dihydroxyphenyl- containing thienopyrimidinones: synthesis of quinazolinone derivatives as novel allosteric inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H

Bioisosteric replacement and scaffold hopping are powerful strategies in drug design useful for rationally modifying a hit compound towards novel lead therapeutic agents. Recently, we reported a series of thienopyrimidinones that compromise dynamics at the p66/p51 HIV-1 reverse transcriptase (RT)-associated Ribonuclease H (RNase H) dimer interface, thereby allosterically interrupting catalysis by altering the active site geometry. Although they exhibited good submicromolar activity, the isosteric replacement of the thiophene ring, a potential toxicophore, is warranted. Thus, in this article, the most active 2-(3,4-dihydroxyphenyl)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one 1 was selected as the hit scaffold and several isosteric substitutions of the thiophene ring were performed. A novel series of highly active RNase H allosteric quinazolinone inhibitors was thus obtained. To determine their target selectivity, they were tested against RT-associated RNA-dependent DNA polymerase (RDDP) and integrase (IN). Interestingly, none of the compounds were particularly active on (RDDP) but many displayed micromolar to submicromolar activity against IN.

Nickel-Catalyzed Synthesis of Quinazolinone Derivatives in Polyethylene Glycol 200

Nickel-Catalyzed Synthesis of Quinazolinone Derivatives in Polyethylene Glycol 200

Synthesis of Quinazolinone Derivatives Catalyzed by Triethanolamine/NaCl in Aqueous Media

ABSTRACTAn eco-friendly advanced strategy developed for the synthesis of quinazolinone derivatives catalyzed by using triethanolamine (TEOA) as a catalyst with the addition of NaCl in presence aqueous media under reflux condition via a one-pot multicomponent reaction. The addition of NaCl controls the formation of micelles and increase the hydrophobic interaction. It is interesting to note that TEOA in combination with NaCl showed excellent selectivity not only in forming the desired product but also in directing the reaction to proceed in a very cleaner way. Valuable features of this protocol including simple reaction condition, excellent yield, broad substrate scope, and easy work-up procedure make this an efficient and promising synthetic approach for the synthesis of quinazolinone derivatives.

Synthesis of 2,3‐Disubstituted Quinazolinone Derivatives through Copper Catalyzed C–H Amidation Reactions

AbstractThe synthesis of quinazolinone derivatives was achieved from 2‐iodobenzamide derivatives and various benzylamines, allylamine, and cinnamylamine derivatives through a one‐pot copper‐catalyzed reaction. In this reaction, the amine component (benzylamine/allylamine/cinnamylamine) is N‐arylated with 2‐iodobenzamide derivatives through Ullman coupling, followed by an intramolecular C–H amidation in the presence of copper catalyst.

Design and Synthesis of Quinazolinone Derivatives as Anti-inflammatory Agents: Pharmacophore Modeling and 3D QSAR Studies

A series of 36 novel substituted quinazolinone derivatives were synthesized and evaluated for their antiinflammatory activity by carrageenan induced paw inflammation model. The ability of these compounds to inhibit cyclooxygenase (COX-1 and 2) enzyme has been determined in-vitro; the results indicated that quinazolinone derivatives were selective towards COX-2 rather than COX-1. Among the quinazolinone derivatives tested, compound 32 showed better inhibition against COX-2 when compared with Celecoxib. Pharmacophore modeling and 3D QSAR studies were performed in order to elucidate structural insights for the anti-inflammatory activity.

ChemInform Abstract: Synthesis of 4‐(3H)‐Quinazolinones by Microwave Assisted Tandem Reaction and Evaluation of Their Antibacterial and Antifungal Activities.

AbstractA one‐pot synthesis of quinazolinone derivatives (IV) (10 examples) from anthranilic acid, primary aromatic amines and Vilsmeier reagent is developed.

Aluminium Nitrate–Catalyzed One-Pot Synthesis of 4(3H)-Quinazolinones by a Three-Component Coupling of Anthranilic Acid, Amines, and Ortho Esters

The one-pot synthesis of quinazolinone derivatives from the reaction of anthranilic acid, amines, and ortho esters in the presence of aluminium nitrate has been carried out. The reaction occurred in a few minutes at room temperature under solvent-free conditions and with excellent yield.

ChemInform Abstract: Microwave‐Assisted Synthesis of Quinazolinone Derivatives by Efficient and Rapid Iron‐Catalyzed Cyclization in Water.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: One‐Pot Synthesis of Quinazolinone Derivatives from Nitro‐Compounds with the Aid of Low‐Valent Titanium.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A novel catalyst zinc(II) perfluorooctanoate [Zn(PFO) 2]-catalyzed three-component one-pot reaction: Synthesis of quinazolinone derivatives in aqueous micellar media

A new type of Lewis acid-surfactant-combined catalyst (LASC), zinc(II) perfluorooctanoate [Zn(PFO) 2], was prepared and applied as a favorable surfactivity catalyst in three-component one-pot cyclocondensation reaction of isatoic anhydride with amines and aldehydes to afford the corresponding quinazolinone derivatives in good yields. Reactions occurred under aqueous micellar media in high atom economy. It was found that this catalyst could be easily quantitatively recovered after the reaction completed and could be reused for at least three cycles without any loss of activity. Furthermore, a mechanism to rationalize the reaction was proposed.