- Design, synthesis, biological evaluation, and molecular docking study of thioxo-2,3-dihydroquinazolinone derivative as tyrosinase inhibitors
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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.
- Adibi, Hossein,Asgari, Mohammad Sadegh,Attarroshan, Mahshid,Farid, Sara Moghadam,Hamedifar, Haleh,Hosseini, Samanesadat,Iraji, Aida,Kabiri, Maryam,Khoshneviszadeh, Mehdi,Larijani, Bagher,Mahdavi, Mohammad,Moayedi, Seyedeh Sara,Moazzam, Ali,Pirhadi, Somayeh,Sakhteman, AmirHossein,Sepehri, Nima
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- Remarkable conversion of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones into the corresponding quinazoline-2,4(1H,3H)-diones: Spectroscopic analysis and X-ray crystallography
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A simple and efficient new synthetic method to obtain 3-substituted quinazolin-2,4-diones 9.16 by the reaction of 3-substituted 2- thioxo-quinazolin-4-ones 1.8 with sodamide under mild conditions was presented. The structure of the newly synthesized compounds was determined by infrared spectroscopy, UV-visible spectroscopy, nuclear magnetic resonance, and single-crystal X-ray crystallographic analysis. The crystal structure of 6-methyl-3-phenylquinazoline-2,4(1H,3H)-dione (11) [C15H12N2O2: MF. 252.27, triclinic, P-1, a = 7.8495 (13) ?, b= 12.456 (2) ?, c = 13.350 (2) ?, α = 103.322 (3)°, β = 90.002 (3)°, γ = 102.671 (4)°, V. 1237.5 (3) ?3, Z= 4, R = 0.0592, wR= 0.1699, S= 1.039] was determined. In the crystal cell, two identical conformers of compound 11 were found connected by intramolecular hydrogen bonds, responsible for the favourable occurrence of these two independent molecules.
- El-Azab, Adel S.,Khalil, Nasr Y.,Abdel-Aziz, Alaa A.-M.
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- Synthesis, biological evaluation and molecular docking of 3-substituted quinazoline-2,4(1H, 3H)-diones
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Abstract: The quinazoline-2,4-diones scaffold is found in bioactive compounds, commercial drugs and exhibit important biological activities. However, their antidiabetic activity is rarely explored. For this purpose, an easy one-pot three-components and straightforward synthesis of 3-substituted quinazoline-2,4-diones was designed, in both, the catalyst- and solvent-free conditions under microwave irradiation. Additionally, the synthesized compounds were screened for in vitro α-amylase and α-glucosidase inhibitory activity, as well as antioxidants and cytotoxicity. The quinazoline-2,4-diones were isolated, with yields in the range of 30-65percent. The compounds 3d, 3e, 3g and 3h displayed moderate activity against α-amylase and/or α-glucosidase enzymes compared with the acarbose drug. The molecular docking study revealed that all active compounds displayed a different type of intermolecular interaction in the pocked site of these enzymes. Interestingly, in the Artemia salina assay, the compound 3d exhibited a higher cytotoxic effect than 5-fluorouracil. All these results support the pharmacological potential of quinazoline-2,4-diones since all evaluated compounds behave as moderate inhibitors of the enzymes α-amylase and/or α-glucosidase. Graphic abstract: An easy one-pot three-components and straightforward synthesis of 3-substituted quinazoline-2,4-diones was designed, in both, the catalyst- and solvent-free conditions under microwave irradiation. Moreover, the in vitro α-amylase and α-glucosidase inhibitory activity, as well as antioxidants and cytotoxicity are reported.[Figure not available: see fulltext.]
- Bastidas, Pedro,Calderón-Zamora, Loranda,García-Páez, Fernando,Ochoa-Terán, Adrián,Osuna-Martínez, Ulises,Picos-Corrales, Lorenzo A,Rendón-Maldonado, Guadalupe,Santos-Ballardo, Lumadhar,Sarmiento-Sánchez, Juan I
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- Synthesis, 2D-QSAR studies and biological evaluation of quinazoline derivatives as potent anti-trypanosoma cruzi agents
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Background: Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease. Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives. Objective: The development of safer and more efficient therapeutic anti-T. cruzi drugs continues to be a major goal in trypanocidal chemotherapy. Method: Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes. Results: Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting toxicity on Vero cells. Conclusion: The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease.
- Battini, Leandro,Bollini, Mariela,Bruno, Ana M.,Casal, Juan J.,Lombardo, María E.,Ni?o, María E.,Puente, Vanesa R.,Sasiambarrena, Leandro D.,Valdez, Damián A. G.
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p. 265 - 276
(2019/07/12)
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- High-selective HDAC6 inhibitor promotes HDAC6 degradation following autophagy modulation and enhanced antitumor immunity in glioblastoma
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Glioblastoma is the most fatal type of primary brain cancer, and current treatments for glioblastoma are insufficient. HDAC6 is overexpressed in glioblastoma, and siRNA-mediated knockdown of HDAC6 inhibits glioma cell proliferation. Herein, we report a high-selective HDAC6 inhibitor, J22352, which has PROTAC (proteolysis-targeting chimeras)-like property resulted in both p62 accumulation and proteasomal degradation, leading to proteolysis of aberrantly overexpressed HDAC6 in glioblastoma. The consequences of decreased HDAC6 expression in response to J22352 decreased cell migration, increased autophagic cancer cell death and significant tumor growth inhibition. Notably, J22352 reduced the immunosuppressive activity of PD-L1, leading to the restoration of host anti-tumor activity. These results demonstrate that J22352 promotes HDAC6 degradation and induces anticancer effects by inhibiting autophagy and eliciting the antitumor immune response in glioblastoma. Therefore, this highly selective HDAC6 inhibitor can be considered a potential therapeutic for the treatment of glioblastoma and other cancers.
- Liu, Jia-Rong,Yu, Chao-Wu,Hung, Pei-Yun,Hsin, Ling-Wei,Chern, Ji-Wang
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p. 458 - 471
(2019/03/23)
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- 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and application thereof
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The invention belongs to the technical field of medicines and relates to 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and an application thereof. 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives comprise stereisomers and pharmaceutically applicable salts of the compounds and have the general structural formula shown in the description, wherein R is described inthe claims and description. The 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives and pharmaceutically applicable acid-added salts of the compounds can be combined with existing medicines or used separately to serve as influenza virus inhibitors to treat influenza and have better curative effects on various type-A influenza in particular.
- -
-
Paragraph 0051; 0055
(2018/04/21)
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- Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate
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A series of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate 10-13a-f has been developed on the basis of the N-chemoselective reaction of 3-substituted quinazoline-2,4-diones 3a-d with ethyl chloroacetate and azide coupling method with amino acid ester hydrochloride. The precursor quinazoline diones 3a-d chemoselective reactions were studied using DFT(B3LYP)/6-311G level of theory and were prepared by a new rearrangement method from the corresponding 2-(3-methyl-4-oxo-3,4- dihydroquinazolin-2-ylthio) acetohydrazide 6. {figure presented}.
- Ismail, El Fekki,Ali, Ibrahim A.I.,Fathalla, Walid,Alsheikh, Amer A.,Tamney, El Said El
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p. 104 - 120
(2017/06/19)
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- Oxidative Rearrangement of Isatins with Arylamines Using H2O2 as Oxidant: A Facile Synthesis of Quinazoline-2,4-diones and Evaluation of Their Antibacterial Activity
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A green and highly efficient synthetic method for the synthesis of quinazoline-2,4-diones with hydrogen peroxide as the terminal oxidant has been developed. The reaction features the mild reaction conditions, broad substrate scope, metal-free catalysts, and sole byproduct water. A plausible mechanism for this process was proposed. Moreover, an antibacterial activity study was performed to evaluate the antimicrobial activities towards two Gram-negative bacterial strains (Escherichia coli, and Klebsiella pneumonia) and two Gram-positive bacterial strains (Staphylococcus epidermidis, and Staphylococcus aureus) using the Broth microdilution method.
- Shi, Guanghao,He, Xinwei,Shang, Yongjia,Yang, Cheng,Xiang, Liwei
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p. 1835 - 1843
(2017/09/06)
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- One-pot Syntheses of Some New 2,4(1H,3H)-quinazolinedione Derivatives in the Absence of Catalyst
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A facile, rapid and one-pot procedure for the synthesis of some new 2,4(1H,3H)-quinazolinediones is described. The method involves the one-pot condensation of isatoic anhydride, primary amine and carbonyl diimidazole (CDI) in the absence of organic or inorganic catalyst. It affords the corresponding product in high yield.
- Mohammadi, Ali Asghar
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p. 2075 - 2078
(2017/05/29)
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- Synthesis, molecular structure and spectroscopic studies of some new quinazolin-4(3H)-one derivatives; An account on the N- versus S-Alkylation
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A new series of N- and S-alkylated products of 3-aryl-1H,3H-quinazolin-2,4-dione and 3-aryl-2-mercapto-3H-quinazolin-4-one, respectively, were prepared in good yields via efficient nucleophilic substitution reaction of the SH and NH substrates with methyl
- Hagar, Mohamed,Soliman, Saied M.,Ibid, Farahate,El Ashry, El Sayed H.
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p. 667 - 679
(2016/01/09)
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- Molecular modeling studies and synthesis of novel methyl 2-(2-(4-Oxo-3-aryl-3,4-dihydroquinazolin-2-ylthio)acetamido)alkanoates with potential anti-cancer activity as inhibitors for methionine synthase
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Cobalamin-dependant cytosolic enzyme methionine synthase (MetS) catalyses the transfer of a methyl group from the methyltetrahydrofolate (MTHF) to homocysteine (Hcy) to produce methionine and tetrahydrofolate (THF). MetS is over-expressed in the cytosol of certain breast and prostate tumour cells. Methionine used as a source of one carbon atom for the building of the DNA of the tumour cells, structural protein and enzymes. In this study, we designed, synthesized and evaluated the cytotoxic activity of a series of substituted methyl 2-(2-(4-oxo-3-aryl-3,4-dihydroquinazolin-2-ylthio)acetamido)acetate and dipeptide that mimic the substructure of MTHF. These inhibitors were docked in to the MTHF binding domain in such the same way as MTHF in its binding domain. The free energies of the binding were calculated and compared to the IC 50 values. This series has been developed by dicyclohexylcarbodiimide (DCC) and azide coupling methods of amino acid esters with carboxylic acid derivatives, respectively. Compound methyl 3-hydroxy-2-(2-(3-(4-methoxyphenyl)- 4-oxo-3,4-dihydroquinazolin-2-ylthio)acetamido)propanoate exhibited the highest IC50 value 20 μg/mL against PC-3 cell line and scored the lowest free energy of the binding (-07.19 kJ/mol).
- Elfekki, Ismail Mahmoud,Hassan, Walid Fathalla Mohamed,Elshihawy, Hosam Eldin Abd Elhamed,Ali, Ibrahim Ahmed Ibrahim,Eltamany, Elsayed Hussein Mostafa
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p. 675 - 694
(2014/08/05)
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- One-step conversion of 2-Amino- N ′-arylbenzamidines into 3-aryl-4-imino-3,4-dihydroquinazoline-2-carbonitriles using 4,5-dichloro-1,2,3- dithiazolium chloride
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2-Amino-N′-arylbenzamidines react with 4,5-dichloro-1,2,3- dithiazolium chloride (Appel salt) in the presence of Huenig's base (2 equiv) to give in one step 3-aryl-4-imino-3,4-dihydroquinazoline-2-carbonitriles in 53-81% yields. Nine examples are presented along with the single-crystal X-ray structure of 4-imino-3-phenyl-3,4-dihydroquinazoline-2-carbonitrile. Furthermore, the behavior of the latter toward both acid and base hydrolysis is investigated. All new compounds are fully characterized, and a mechanistic rationale for the formation of the iminoquinazolines is provided.
- Mirallai, Styliana I.,Manos, Manolis J.,Koutentis, Panayiotis A.
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p. 9906 - 9913
(2013/10/22)
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- Synthesis and spectral characterisation of novel 2,3-disubstituted quinazolin-4(3H)-one derivatives
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A new series of 2,3-disubstituted quinazolinones was synthesised via the reaction of readily obtainable 2-thioxo-3-phenylquinazolin-4(3H)-one 1 with ethyl chloroacetate followed by hydrazinolysis to afford the hydrazide 3. This was allowed to react with d
- Mahmoud, Mahmoud R.,Abou-Elmagd, Wael S.I.,Abdelwahab, Salwa S.,Soliman, El-Sayed A.
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experimental part
p. 66 - 71
(2012/05/04)
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- Green synthesis of quinazolinone derivatives catalyzed by iodine in ionic liquid
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A series of quinazolinone derivatives were synthesized by the reaction of 2-aminobenzamides and triethyl orthoformate or triphosgene in ionic liquid of [BMIm]BF4 at 80 °C catalyzed by iodine in good yields. Compared to other methods, this new procedure has the advantages of mild reaction conditions, good yields, operational simplicity, and environmentally friendly procedure. Copyright Taylor & Francis Group, LLC.
- Wang, Shu-Liang,Yang, Ke,Yao, Chang-Sheng,Wang, Xiang-Shan.
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experimental part
p. 341 - 349
(2011/11/12)
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- Molybdenum-mediated synthesis of quinazolin-4(3H)-ones via cyclocarbonylation using microwave irradiation
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A new, efficient and practical synthesis of quinazolin-4(3H)-ones is reported via molybdenum-mediated cyclocarbonylation using microwave irradiation. These methods allow access to a wide range of quinazolin-4(3H)-ones in reasonable yields without the need for gaseous carbon monoxide and palladium catalysts. A range of reactions illustrating the wide scope of this chemistry was carried out and all proceeded in reasonable yields.
- Roberts, Bryan,Liptrot, David,Luker, Tim,Stocks, Michael J.,Barber, Catherine,Webb, Nicola,Dods, Robert,Martin, Barrie
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p. 3793 - 3796
(2011/08/06)
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- Reaction of 3-hydroxyquinoline-2,4-diones with isocyanates and thermally induced transformation of the reaction products
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3-Hydroxyquinoline-2,4-diones 1 react with isocyanates to give novel 1,2,3,4-tetrahydro-2,4-dioxoquinolin-3-yl (alkyl/aryl)carbamates 2 and/or 1,9b-dihydro-9b-hydroxyoxazolo[5,4-c]quinoline-2,4(3aH,5H)-diones 3. Both of these compounds are converted, by boiling in cyclohexylbenzene solution in the presence of Ph3P or 4-(dimethylamino)pyridine, to give 3-(acyloxy)-1,3-dihydro-2H-indol-2-ones 8. All compounds were characterized by IR, and 1H- and 13C-NMR spectroscopy, as well as by EI mass spectrometry. Copyright
- Mrkvicka, Vladimir,Lycka, Antonin,Vicha, Robert,Klasek, Antonin
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experimental part
p. 78 - 91
(2011/03/16)
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- Metal and phosgene-free synthesis of 1H-quinazoline-2,4-diones by selenium-catalyzed carbonylation of o-nitrobenzamides
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1H-Quinazoline-2,4-diones were efficiently synthesized by selenium-catalyzed carbonylation of o-nitrobenzamides under relatively mild conditions. In situ-generated carbonyl selenide (SeCO) is proposed to initiate the catalytic carbonylation. Thus, a concise transition metal and phosgene-free synthetic route to potentially bioactive-substituted 1H-quinazoline-2,4-dione derivatives has been developed.
- Wu, Xiaowei,Yu, Zhengkun
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experimental part
p. 1500 - 1503
(2010/04/29)
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- Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction
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Novel derivatives of 5-(substituted)benzylidene-3-(4-substituted)phenylsulfonylimidazolidine-2,4-diones (3a-r), 1-(4-substituted)phenylsulfonyl-3-(4-substituted)phenylpyrimidine-2,4,6-(1H,3H,5H)-triones (6a-l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1H,3H)- diones (8a-l) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from 9 different organs. The tested compounds have showed good inhibitory effect at the ovarian cancer (IGROV1) cell line. A significant inhibition for (RXF393) renal cancer cells was observed with series 3 compounds, while in the other two series 6 and 8, there was a significant inhibition of ovarian cancer cells (OVCAR-8) and melanoma cells (SK-MEL-2). Interestingly; beside the strong inhibition of compound 3q to IGROV1 and RXF393 cells, a great inhibition (199.62%) for (M14) Melanoma cells was observed at the tested concentration (10?μM). ADME-T and pharmacophore prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.
- El-Deeb, Ibrahim M.,Bayoumi, Said M.,El-Sherbeny, Magda A.,Abdel-Aziz, Alaa A.-M.
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scheme or table
p. 2516 - 2530
(2010/07/05)
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- 3-aryl(alkyl)quinazoline-2,4(1H,3H)-diones and their alkyl derivatives
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Two-stage reaction of methyl anthranilate with aryl(alkyl) isocyanates in keeping with the quantumchemical calculations and XRD analysis resulted in 3-aryl(alkyl)quinazoline-2,4(1H,3H)-diones that by treatment with alkyl halides, phenacyl bromides, esters
- Shestakov,Sidorenko,Bushmarinov,Shikhaliev,Antipin
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experimental part
p. 1691 - 1696
(2010/04/29)
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- Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton
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Novel non-steroidal progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton were developed and their structure-activity relationships were investigated. Among the prepared compounds, 4-(4,4-diethyl-3,
- Nakagawa, Aya,Uno, Shigeyuki,Makishima, Makoto,Miyachi, Hiroyuki,Hashimoto, Yuichi
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p. 7046 - 7054
(2008/12/22)
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- Synthesis, properties, and mass-spectrometric fragmentation of 2-thio derivatives of 3-arylquinazolin-4-ones
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We have studied the reactions of alkylation, oxidation, and hydrolysis of 3-aryl-2-thioxoquinazolin-4-ones. Alkylation in an alkaline medium occurs exclusively at the sulfur atom. Oxidation by hydrogen peroxide leads to formation of 3-arylquinazoline-2,4-diones. The latter are also obtained in base or acid hydrolysis of the synthesized S-alkyl derivatives. When 3-aryl-2-thioxoquinazolin-4-ones are reacted with iodine, we obtain the disulfides, while the reaction with chlorine in hydrochloric acid leads to 2-chloroquinazolin-4-ones. Studying the mass spectrometric behavior of the compounds obtained made it possible to observe in the gas phase ring-chain isomerization of the heterocyclic ring, and also S-N migration of the propargyl radical in molecular ions of the S-propargyl derivatives.
- Azev,Golomolzin,Dyulcks,Klyuev,Yatluk
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p. 356 - 361
(2008/09/21)
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- Tandem palladium-catalyzed urea arylation-intramolecular ester amidation: Regioselective synthesis of 3-alkylated 2,4-quinazolinediones
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(Chemical Equation Presented) o-Halo benzoates can be combined with monoalkyl ureas in a tandem palladium-catalyzed arylation-ester amidation sequence to deliver quinazolinedione products. The reactions are regioselective for formation of the 3-N-alkyl isomers. Significant variation of both coupling partners is possible, allowing the synthesis of a diverse array of substituted quinazolinediones, exemplified by the preparation of a simple unsymmetric-dialkylated natural product.
- Willis, Michael C.,Snell, Robert H.,Fletcher, Anthony J.,Woodward, Robert L.
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p. 5089 - 5091
(2007/10/03)
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- Synthesis of some new quinazoline derivatives analogues to MKC-442 and TNK 561
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A series of different acyclo quinazoline nucleosides 6, 7, 8, 10, 12, 13, and 14 have been synthesized. The site of glycosylation was confirmed by 1H-NMR and 13C-NMR spectroscopy.
- El-Hamid, Abd,Ismail,Attia, Adel M. E.
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p. 1231 - 1240
(2007/10/03)
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- New compounds derived from quinazoline
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A compound selected from those of formula (I): wherein A, B, D, X, R1, R2, m and n are as defined in the description, their diastereoisomers and addition salts thereof with a pharmaceutically acceptable acid or base.
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- Specific nonpeptide inhibitors of puromycin-sensitive aminopeptidase with a 2,4(1H,3H)-quinazolinedione skeleton.
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Potent, specific, chemically stable and non-peptide/small-molecular inhibitors of puromycin-sensitive aminopeptidase, such as 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (PAQ-22, 5), were prepared by the structural development of a potent PSA inhibitor, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22, 4). The design was carried out partly by applying electrostatic potential field information obtained from PIQ-22 (4) and its derivatives based on thalidomide (2). This information revealed that a positive electrostatic potential field around the benzylic methylene in the tetrahydroisoquinoline ring is necessary for potent activity. Lineweaver-Burk plot analysis showed that PAQ-22 (5) and its derivatives inhibit puromycin-sensitive aminopeptidase (PSA) in a non-competitive manner. These potent and specific PSA inhibitors showed dose-dependent cell invasion-inhibitory activity in a Matrigel assay using mouse melanoma B16F10/L5 cells, in spite of their low cell toxicity.
- Kakuta, Hiroki,Tanatani, Aya,Nagasawa, Kazuo,Hashimoto, Yuichi
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p. 1273 - 1282
(2007/10/03)
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- An efficient one-pot procedure for preparation of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazolinone derivatives under microwave irradiation
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An efficient one-pot synthesis of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazolinone derivatives are given by the condensation of isatoic anhydride, primary amine and urea or thiourea in the absence of organic or inorganic reagents under microwave irr
- Azizian, Javad,Mohammadi, Ali A.,Karimi, Ali R.
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p. 415 - 420
(2007/10/03)
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- Synthesis and X-ray characterisation of a new polycondensed heterocycle obtained by a novel Mn(III)-mediated cascade reaction of 2-cyanophenyl isothiocyanate
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2-Cyanophenyl isothiocyanate reacted with Mn(III) acetate in acetic acid or acetonitrile to give fair yields of a new polycondensed heterocycle arising from the joining together of two molecules of the starting isothiocyanate with loss of a CS moiety. The yields were close to 90% when the reaction was carried out in the presence of diethyl malonate. This compound was unambiguously identified by X-ray crystallography. Under the same conditions, 2-(methoxycarbonyl)phenyl isothiocyanate gave a quinazolinimine derivative instead which is likely to arise from cyclisation of an intermediate N,N′-diarylthiourea. The mechanism of formation of the former compound probably involves formation of a N,N′-bis(2-cyanophenyl)thiourea, followed by rearrangement and radical tandem ring closure of the corresponding cyclic imine derivative. This hypothesis is also supported by semiempirical calculations.
- Calestani, Gianluca,Capella, Laura,Leardini, Rino,Minozzi, Matteo,Nanni, Daniele,Papa, Romina,Zanardi, Giuseppe
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p. 7221 - 7233
(2007/10/03)
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- Rearrangement of 4-imino-(1H,4H)-3,1-benzoxazine-2-ones to 2,4- quinazolinediones via an isocyanate carboxamide intermediate
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Reaction of 3-arylimino-2-indolinones 1 with m-chloroperbenzoic acid in CH2Cl2 or methanol at 0°C leads to the corresponding 3-aryl-2,4(1H,3H)- quinazolinediones 4 and (2-arylcarbamoyphenyl)carbamic acid methyl ester 5, respectively.
- Azizian, Javad,Mehrdad, Morteza,Jadidi, Khosrow,Sarrafi, Yaghob
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p. 5265 - 5268
(2007/10/03)
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- Palladium-Catalyzed Cyclocarbonylation of o-Iodoanilines with Heterocumulenes: Regioselective Preparation of 4(3H)-Quinazolinone Derivatives
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A catalyst system comprising palladium acetate - bidentate phosphine is effective for the cyclocarbonylation of o-iodoanilines with heterocumulenes at 70-100°C for 12-24 h to give the corresponding 4(3H)-quinazolinone derivatives in good yields. Utilizing o-iodoaniline with isocyanates, carbodiimides, and ketenimines for the reaction, 2,4-(1H,3H)-quinazolinediones, 2-amino-4(3H)-quinazolinones and 2-alkyl-4(3H)-quinazolinones were obtained, respectively. The nature of the substrates including the electrophilicity of the carbon center of the carbodiimide, and the stability of the ketenimine, influence the product yields of this reaction. Urea-type intermediates are believed to be generated first in situ from the reaction of o-iodoanilines with heterocumulenes, followed by palladium-catalyzed carbonylation and cyclization to yield the products.
- Larksarp, Chitchamai,Alper, Howard
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p. 2773 - 2777
(2007/10/03)
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- Relationships between the chemical structure of substances and their antimycobacterial activity against atypical strains. Part 18. 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and isosteric 3-phenylquinazoline-2,4(1H,3H)-diones
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A series of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 and 3-phenylquinazoline-2,4(1H,3H)-diones 5 substituted on the phenyl rings were synthesized. The target compounds as well as the intermediates were tested against Mycobacterium tuberculosis, M. kansasii, and M. avium. The replacement of the oxygen atom by nitrogen resulted in a decrease or loss of antimycobacterial activity. 2-[(Ethoxycarbonyl)amino]benzanilides 4 appeared to be inactive. Salicylanilides 1 and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 exhibit significant activity against both M. tuberculosis and nontuberculous mycobacteria (the MICs within the range of 4-250 μmol/l for all compounds). The antimycobacterial activity of the compounds increases with increasing both electron-withdrawing properties and hydrophobicity of the substituent(s) on the phenyl moiety. The antimycobacterial profile of the compounds was analyzed according to the criteria based on vector algebra, such as cosine coefficients. Moreover, salicylanilides 1 exhibit activity against other microorganisms tested by the agar diffusion method.
- Waisser, Karel,Machacek, Milos,Dostal, Hynek,Gregor, Jiri,Kubicova, Lenka,Klimesova, Vera,Kunes, Jiri,Palat Jr., Karel,Hladuvkova, Jana,Kaustova, Jarmila,Moellmann, Ute
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p. 1902 - 1924
(2007/10/03)
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- Synthesis and anticonvulsant activity of new acylthiosemicarbazides and thiazolidines
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A number of 1-(3-phenyl-4(3H)-quinazolinone-2-ylmercaptoacetyl)-4-substituted thiosemicarbazide and 2-(3-phenyl-4(3H)-quinazolinone-2-ylmercaptoacetylhydrazono)-3-substit uted 4-thiazolidone derivatives were synthesized and evaluated for anticonvulsant ac
- Gursoy,Karali
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p. 857 - 866
(2007/10/03)
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- Aldose reductase inhibition by 2,4-oxo and thioxo derivatives of 1,2,3,4-tetrahydroquinazoline
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Inhibitors of aldose reductase are believed to be useful for the treatment of diabetic complications.Original acetic acids and their thioxo derivatives have been synthesized and examined for their ability to inhibit aldose reductase in vitro and in vivo.Most were active in vitro on rat lens aldose reductase in the 10-7 molar range.Compound V16, which has a (2'-fluoro-4'-bromo)benzyl substituent on nitrogen N-3 was found in hypergalactosemic rats to be a good inhibitor of galactitol accumulation in sciatic nerves andto prevent cataract formation.
- Billon, Florence,Delchambre, Chantal,Cloarec, Alix,Sartori, Eric,Teulon, Jean-Marie
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p. 121 - 126
(2007/10/02)
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- Structure of the 2-Isocyanatobenzoyl Chloride-Aluminium Chloride (1:2) Complex: Reactions with Some Nucleophiles
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The reactions of 2-isocyanatobenzoyl chloride-aluminium chloride (1:2) complex with methanol, aniline, methyl anthranilate, ethyl anthranilate, 2-aminobenzophenone, 2-amino-5-chlorobenzophenone have been studied.Based on the products obtained in these reactions, the 1:2 complex has been shown to be a mixture of acyclic and cyclic structures (4) and (5) respectively.This is in accordance with the observations recorded in IR studies.
- Acharya, Baman P.,Rao, Y. Ramachandra
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p. 1133 - 1139
(2007/10/02)
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- Synthesis of 3-Aryl-1H,3H-quinazolin-2,4-diones and Their 2-Thio Analogues
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3-Aryl-(2-thio)-1H,3H-quinazolin-2,4-diones (3, R= H, CH3, C2H5; X= O, S) have been obtained by the fusion of isatoic anhydrides (1, R= H, CH3, C2H5) with aryliso(thio)cyanates (2, X= O, S).
- Reddy, Ch. K.,Reddy, P. S. N.,Ratnam, C. V.
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p. 882 - 883
(2007/10/02)
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- Mechanisms of the Reactions of Benzoazetinones with Nucleophiles: Evidence for an Imino Ketene Intermediate
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From studies of the kinetics of the reactions of N-tert-butylbenzoazetinone (3a) with diethylamine and with alcohols to give the ring-opened adducts 4, the presence of a trace equilibrium component, the more electrophilic imino ketene 2a, has been inferre
- Olofson, R. A.,Vander Meer, Robert K.
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p. 3377 - 3379
(2007/10/02)
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- Reactions and Rearrangement of 2,4-Quinazolinediones. An Efficient Simple Synthesis of 3-Amino-1H,3H-quinazolinedione
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An efficient synthesis of 3-amino-1H,3H-quinazolinedione by the action of hydrazine on the readily accessible 3-phenyl-2,4(1H,3H)-quinazolinedione and 2-anilino-4H-3,1-benzoxazin-4-one are described.
- Badawy, M. A.,Ibrahim, Yehia A.
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p. 1403 - 1404
(2007/10/02)
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- Imides: Part IV - Synthesis and Reactions of N-(Arylsulphonyloxy)cyclohex-4-ene-1,2-dicarboximides
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N-(Arylsulphonyloxy)cyclohex-4-ene-1,2-dicarboximides (IIa and IIb) undergo base-catalysed Lossen rearrangement with aromatic amines in refluxing ethanol to give mixtures of N-(2-arylcarbamoyl)cyclohex-4-enyl-N'-arylureas (IIIa-d) and the amine salts of arylsulphonic acids (IVa-h).Fusion of II with aromatic amines for 15 min gives mixtures of 3-arylquinazoline-2,4-diones (VIa-c) and IV; however fusion for 1 hr affords mixtures of sym-N,N'-diarylureas (VIIa-d) and IV.Compounds IIa and IIb also react with phenylhydrazine to give mixtures of VIII and phenylhydrazine saltof arylsulphonic acids (IXa and IXb).The mass spectra of IIb and IIIa are presented, and discussed.
- Aly, N. F.,El-Komy, M.,Aly, N. Y.,Orabi, M. O. A.
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p. 471 - 476
(2007/10/02)
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- Convenient Preparation of N-substituted 2-Amino-4H-3,1-benzoxazin-4-ones and 3-Substituted 2,4(1H,3H)-Quinazolinediones
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Room temperature of 2-(3-arylureido)benzoic acids (1) and methyl2-(3-alkyl-, or 3-arylureido)-benzoates (2) with concentrated sulfuric acid leads to N-substituted 2-amino-4H-3,1-benzoxazin-4-ones (3) in generally very good yields.The isomeric 3-substitute
- Papadopoulos, E. P.,Torres, C. D.
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p. 269 - 272
(2007/10/02)
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- HETEROCYCLIZATION WITH IMINIUM CHLORIDES, II. SYNTHESIS OF 4H--BENZOXAZINE-4-ONES AND QUINAZOLINONES
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Reactions between methyl anthranilate and a variety of PI salts afforded 2-ammonio-4H--benzoxazine-4-one chlorides which were subjected to nucleophilic reactions.With primary amines, 2-ureidoanthraniloyl amides were obtained, which were smoothly cyclized in boiling acetic anhydride or dimethylformamide to give 1H,3H-quinazoline-2,4-diones.
- Bitter, I.,Szoecs, L.,Toeke, L.
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