21038-90-4

Upstream product

• 118-48-9 isatoic anhydride 
• 2253-73-8 isopropyl isothiocyanate 
• 118-92-3 anthranilic acid 
• 5943-91-9 3-isopropylquinazoline-2,4(1H,3H)-dione 
• 75-15-0 carbon disulfide 
• 75-31-0 isopropylamine 
• 610-94-6 2-bromobenzoic acid methyl ester 
• 333-20-0 potassium thioacyanate 
• 30391-89-0 2-amino-N-isopropylbenzamide 

Relevant academic research and scientific papers

Design, synthesis, biological evaluation, and molecular docking study of thioxo-2,3-dihydroquinazolinone derivative as tyrosinase inhibitors

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.

The natural-based optimization of kojic acid conjugated to different thio-quinazolinones as potential anti-melanogenesis agents with tyrosinase inhibitory 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.

Design, synthesis, in vitro and in silico biological assays of new quinazolinone-2-thio-metronidazole derivatives

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.

Novel quinazolin–sulfonamid derivatives: synthesis, characterization, biological evaluation, and molecular docking studies

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.

CuBr-catalysed one-pot multicomponent synthesis of 3-substituted 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives

A novel methodology is presented for the synthesis of 3-substituted 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives based on an efficient tandem multicomponent reaction using copper bromide as catalyst. This methodology is based on the multicomponent one-pot reaction of methyl 2-bromobenzoate, phenylisothiocyanate derivatives and sodium azide in the presence of copper bromide and l-proline under basic conditions. To show the generality of the method, various phenylisothiocyanates bearing electron-donating or electron-withdrawing functionalities were used and the desired products were obtained in high isolated yields.

A green and efficient synthesis of 2-thioxoquinazolinone derivatives in water using potassium thiocyanate

Green chemistry is one of the most important routes for the synthesis of heterocyclic compounds. In this regard, the synthesis of 2-thioxoquinazolinone derivatives was achieved by condensation of versatile materials including isatoic anhydride, amine and potassium thiocyanate in the green medium of water. This convenient and ef?cient method affords the desired products with good to excellent yields.

Convenient and sequential one-pot route for synthesis of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives

A new and efficient synthetic process has been developed for preparation of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives. The related products were synthesized through reaction of isatoic anhydride, amines/anthranilic acids, and carbon disulfide (CS2) in the presence of potassium hydroxide in ethanol at reflux. Graphical abstract: [Figure not available: see fulltext.]

Development of thioquinazolinones, allosteric Chk1 kinase inhibitors

A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at Km for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site ～13 A from the ATP binding site. Preliminary data is presented for several of these compounds.