21263-59-2

Electrophilic heterocyclization of 5-alkenyl-1-methyl-6-thioxopyrazolo[3,4-d]pyrimidin-4-ones and 3-alkenyl-2-thioxoquinazoline-4-ones under the action of p-alkoxyphenyltellurium trichloride leads to annulation of thiazoline cycle with formation of 7-[(p-alkoxyphenyl)telluromethyl]-1-methyl-6,7-dihydropyrazolo[3,4-d][1,3]thiazolo[3,2-a]pyrimidin-4(1H)-ones hydrochlorides and 2-(p-alkoxyphenyl)dichlorotelluromethyl-2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-ones hydrochlorides. Reduction of salts by the action of excess of sodium sulfite leads to formation of arylhetaryl telluride.

In this study, deep eutectic solvents (DESs) were used as green and eco-friendly media for the synthesis of substituted 2-mercaptoquinazolin-4(3H)-ones from different anthranilic acids and aliphatic or aromatic isothiocyanates. A model reaction on anthranilic acid and phenyl isothiocyanate was porformed in 20 choline chloride-based DESs at 80 °C to find the best solvent. Based on the product yield, choline chloride-urea (1:2) DES was found to be the most effective, while DESs acted both as solvents and catalysts. Desired compounds were prepared with moderate to good yields using stirring, microwave-assisted, and ultrasound-assisted synthesis. Significantly, higher yields were obtained with mixing and ultrasonication (16-76%), while microwave-induced synthesis showed lower effectiveness (13-49%). The specific contribution of this research is the use of DESs in combination with the above-mentioned green techniques for the synthesis of a wide range of derivatives. The structures of the synthesized compounds were confirmed by1H and13C NMR spectroscopy.

A new series of quinazoline-4-one/chalcone hybrids, 7–26, was synthesized in this study as EGFR inhibitors with antiproliferative activity. Target compounds were synthesized and in vitro tested against different cancer cell lines, EGFR, and BRAF enzymes.

Tyrosinase is known to be a key enzyme in melanogenesis and hyperpigmentation. In this study, a series of thioxo-dihydroquinazolinone compounds were designed and synthesized as tyrosinase inhibitors. Among the investigated compounds, 4m demonstrated the best inhibitory activity with an IC50 value of 15.48 μM compared to kojic acid as a positive control with IC50 value of 9.30 μM. In kinetic evaluation against tyrosinase, 4m depicted a mixed inhibition pattern. Additionally, antioxidant evaluations exhibited moderate to weak potency in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The detailed interactions and binding mode toward tyrosinase of the most potent derivative were explicated by molecular docking study. Moreover, the computer-aided drug-likeness and pharmacokinetic studies were also carried out.

Abstract: In the present study, we have synthesized a series of novel 2-(3-substituted-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-diones by the reaction of 3-(substituted)-2-hydrazino-quinazoline-4(3H)-ones with phthalic anhydride. The starting material 3-(substituted)-2-hydrazino-quinazolin-4(3H)-ones were synthesized from various primary amines. All the synthesized compounds were screened for their antitubercular, anti-HIV and antibacterial activity against different gram positive and gram negative strains by agar dilution method. Among the test compounds, 2-(3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-dione (QCT7) shown most potent antibacterial activity against E. coli, and S. aureus with the MIC of 3 μg/mL. The compound QCT7 exhibited the antitubercular activity with the MIC of 25 μg/mL and anti-HIV activity with the EC50 of 43.68 μM against HIV1 and HIV2 and offers potential lead for further optimization and development to new antitubercular and anti-HIV agents. The results obtained from this study confirm that the synthesized and biologically evaluated quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities and are new scaffolds for antimicrobial activity.

Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC50 value of 0.46 and 0.50 μM, respectively. In kinetic evaluation against tyrosinase, 5j depicted an uncompetitive inhibition pattern. Designed compounds also exhibited mild antioxidant capacity. Moreover, 5j and 5h achieved good potency against the B16F10 cell line to reduce the melanin content, whilst showing limited toxicity against malignant cells. The proposed binding mode of new inhibitors evaluated through molecular docking was consistent with the results of structure–activity relationship analysis.

A new series of quinazolinone-2-thio-metronidazole derivatives 9a-o was designed, synthesized and assayed for their activities against metabolic enzymes human carbonic anhydrase I and II (hCAs I and II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against CA enzymes, 4-fluorophenyl derivative 9i, was 4 and 7-times more potent than standard inhibitor acetazolamide against hCA I and II, respectively; 4-fluorobenzyl derivative 9m as the most potent compound against cholinesterase enzymes, was around 11 and 21-times more potent than standard inhibitor tacrine against AChE and BChE, respectively; the most active α-glucosidase inhibitor 9h with 4-methoxyphenyl moiety was 5-times more active that acarbose as standard inhibitor. Furthermore, in order to study interaction modes of the most potent compounds in the active site of their related enzymes, molecular modeling was performed. Druglikeness, ADME, and toxicity profile of the compounds 9i, 9m, and 9h were also predicted.

In the design of novel drugs, the formation of hybrid molecules via the combination of several pharmacophores can give rise to compounds with interesting biochemical profiles. A series of novel quinazolin–sulfonamid derivatives (9a–m) were synthesized, characterized and evaluated for their in vitro antidiabetic, anticholinergics, and antiepileptic activity. These synthesized novel quinazolin–sulfonamid derivatives (9a–m) were found to be effective inhibitor molecules for the α-glycosidase, human carbonic anhydrase I and II (hCA I and hCA II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzyme, with Ki values in the range of 100.62 ± 13.68–327.94 ± 58.21 nM for α-glycosidase, 1.03 ± 0.11–14.87 ± 2.63 nM for hCA I, 1.83 ± 0.24–15.86 ± 2.57 nM for hCA II, 30.12 ± 3.81–102.16 ± 13.87 nM for BChE, and 26.16 ± 3.63–88.52 ± 20.11 nM for AChE, respectively. In the last step, molecular docking calculations were made to compare biological activities of molecules against enzymes which are achethylcholinesterase, butyrylcholinesterase and α-glycosidase. Communicated by Ramaswamy H. Sarma.

In the present study, we have synthesized a series of novel 2-phenyl-3-(substituted quinazolinylamino)quinazolin-4(3H)-ones by the reaction of 3-(substituted)-2-hydrazinoquinazoline-4(3H)-ones with 2-phenyl-3,1-benzoxazin-4-one. The starting material 3-(substituted)-2-hydrazino-quinazolin-4(3H)-ones were synthesized from various primary amines. All the synthesized compounds were screened for their antitubercular, anti-HIV and antibacterial activity against different Gram-positive and Gram-negative strains by agar dilution method. Among the test compounds, 3-(4-nitrophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one (BQZ6) and 3-(4-chlorophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one (BQZ7) shown most potent antibacterial activity against E. coli, P. aeruginosa and S. aureus with the MIC of 3 μg/mL. The compound BQZ7 exhibited the antitubercular activity with the MIC of 25 μg/mL and anti-HIV activity with the MIC of 35.4 μg/mL against HIV1 and HIV2 and offers potential lead for further optimization and development to new antitubercular and anti-HIV agents. The results from this study confirm that the synthesized and biologically evaluated quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities and are new scaffolds for antimicrobial activity.

Quinazolines were surveyed as biologically relevant moieties against different cancer cell lines, so in the present study, we analyzed novel derivatives as target-oriented chemotherapeutic anti-cancer drugs. A series of 3-substituted 2-thioxo-2,3-dihydro-1H-quinazolin-4-ones 4a-e were synthesized via the reaction of 2-aminobenzoic acid (1) with isothiocyanate derivatives 2a-e. S-alkylation and S-glycosylation were carried via the reaction of 4a-e with alkyl halides and α-glycopyranosyl bromides 7a,b under anhydrous alkaline and glycoside conditions, respectively. The S-alkylated and S-glycosylated structures, and not that of the N-alkylated and N-glycosylated isomers, have been selected for the products. Conformational analysis has been studied by homo- and heteronuclear two-dimensional NMR methods (DQF-COSY, HMQC, and HMBC). The S site of alkylation and glycosylation were determined from the 1H, 13C heteronuclear multiple-quantum coherence (HMQC) experiments. All derivatives were subjected to molecular docking calculations, which selected some derivatives (5n, 8c, 8g, 9c, and 9a) as promising ones based on their excellent binding affinities towards the EGFR tyrosine kinase molecular target. The in vitro cytotoxic activity against MCF-7 and HepG2 cell lines showed effective anti-proliferative activity of the analyzed derivatives with lower IC50 values especially 9a with IC50 = 2.09 and 2.08 μM against MCF-7 and HepG2, respectively, and their treatments were safe against the normal cell line Gingival mesenchymal stem cells (GMSC). Moreover, RT-PCR reaction investigated the apoptotic pathway for the compound 9a, which activated the P53 genes and its related genes. So, further work is recommended for developing it as a chemotherapeutic drug.

A series of 3-substituted-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones and 6-iodo-3-substituted-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones were synthesized in choline chloride/urea deep eutectic solvent. Substituted 2-mercapto-4(3H)-quinazolinones were synthesized from anthranilic acid or 5-iodoanthranilic acid and appropriate isothiocyanates in good to excellent yields. Isolation of final product was easy and required no further purification. Synthesis of these compounds was rapid, selective, and catalyst free, while preparation of deep eutectic solvent was easy, components are readily available, cheap, and environmentally friendly.

Synthesis of thiazoles was carried out from allyl thioureas using different cyclizing agents such as hydrogen chloride gas and bromine. Synthesized compounds were characterized by IR, 1H and 13C NMR, mass spectrometry, and elemental analysis. The synthesized thiazoles were evaluated for their antibacterial activity against Gram postitive (Lactobacillus bulgaris and Streptococcus mitis) and Gram negative (Yersinia) as well as antifungal activity against Aspergillus niger fungi.

Substituted o-Amino-N-(prop-2-yn-1-yl) aromatic amides easily reacted with carbon disulfide (CS2) in the presence of potassium hydroxide (KOH) in EtOH under reflux conditions. Cyclization reaction followed by a favored 5-exo-dig ring closure af

A robust 'catch and release' synthesis of fused 2-alkylthio-3-substituted-pyrimidinones mediated by the polymer-bound base P-BEMP is described. This reengineered synthesis combines the efficiency of the classical synthesis (three steps, three diversity points) with the practical benefits of resin-bound reagents. The solution-phase strategy, reagent compatibility, and the results of a representative 48-member combinatorial library are described and presented herein.

The synthesis of chiralic propionic acid ethylesters of 3-alkyl-4-oxo- 2-thioxo-1,2,3,4-tetrahydroquinazolines was described and their chromatographic behaviour was investigated on the chiralic phases (S,S)- Whelk-01 and Chiralcel-OD-H. The enantioselective cleavage succeeded by means of lipase of Candida cylindracea (CCL, E.C. 3.1.1.3.), of pork liver esterase (PLE, E.C. 3.1.1.1.) and of the enzymes of screening set Chirazyme, too. The results pointed out that the modification at the C3-alkyl group has a significant influence to the cleavage rate and the enantioselectivity. The highest selectivity is to obtain in presence of π-electrons in the 3- substituent whereas voluminous aryl groups block up the effectiveness of the enzymes used.

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Compounds of the formula: STR1 wherein X is independently halogen, lower alkyl of 1 to 6 carbon atoms, lower alkoxy of 1 to 6 carbon atoms, nitro, lower alkylsulfinyl of 1 to 6 carbon atoms, lower alkylthio of 1 to 6 carbon atoms, amino or trifluoromethyl; n is 0, 1, 2 or 3; R is hydrogen, alkyl of 1 to 10 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, lower alkenyl of 2 to 6 carbon atoms, or lower alkynyl of 2 to 6 carbon atoms, all optionally substituted with 1 to 3 of the same or different halogen atoms; or aryl of 6 to 12 carbon atoms; or substituted aryl substituted with 1 to 3 substituents independently selected from lower alkyl of 1 to 4 carbon atoms, lower alkoxy of 1 to 4 carbon atoms, and the group --S(O)k R2 where k is 0, 1 or 2 and R2 is lower alkyl of 1 to 4 carbon atoms, nitro, cyano or halogen; and R1 is lower alkyl of 1 to 6 carbon atoms, lower cycloalkyl of 3 to 8 carbon atoms or aryl of 6 to 12 carbon atoms, provided that R and R1 are not both cyclohexyl, are fungicidal and in some cases insecticidal.

Compounds of the formula: STR1 wherein X is independently halogen, lower alkyl of 1 to 6 carbon atoms, lower alkoxy of 1 to 6 carbon atoms, nitro, the group R1 --S(O)m -- wherein R1 is lower alkyl of 1 to 6 carbon atoms and m is 0, 1 or 2, amino, or trifluoromethyl; n is 0, 1, 2 or 3; and R is alkyl of 1 to 10 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; lower alkenyl of 2 to 6 carbon atoms; or lower alkynyl of 2 to 6 carbon atoms, all optionally substituted with 1 to 3 of the same or different halogen atoms, or aryl of 6 to 12 carbon atoms or substituted aryl substituted with 1 to 3 groups independently selected from lower alkyl of 1 to 4 carbon atoms, lower alkoxy of 1 to 4 carbon atoms, lower alkylthio of 1 to 4 carbon atoms, oxidized alkylthio, nitro, cyano, or halogen are fungicidal.