- Synthesis of quinazoline-2,4(1H,3H)-dione from carbon dioxide and 2-aminobenzonitrile using mesoporous smectites incorporating alkali hydroxide
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A series of magnesium containing mesoporous smectites has been prepared with and without incorporation of alkali hydroxide (NaOH, KOH or LiOH) and employed for the reaction of CO2 with aminobenzonitrile to produce quinazoline-2,4(1H,3H)-dione. The effects of the quantity and kind of the incorporated alkali atoms on the catalytic properties of the smectites were investigated. Characterization of the smectites has shown that the incorporation of alkali atoms reduces their surface area and total pore volume but enhances the amount and strength of their basic sites. The product yield increases with the amount of alkali atoms incorporated. The incorporation of Li was less effective than that of Na and K for the enhancement of the yield. It has been suggested that weak and/or moderate base sites are responsible for the reaction. The active sites should be alkali hydroxide particles existing between the smectite layers for the alkali incorporated smectites, while for the un-incorporated smectite, the active sites should be the Mg atoms and/or the neighboring O atoms. The Na incorporated smectite was deactivated by repeated catalyst recycling, while such deactivation was not observed with the un-incorporated smectite. The reason for the deactivation was discussed in connection with the structures of the active sites and the actions of the reaction intermediate. This journal is the Partner Organisations 2014.
- Fujita, Shin-Ichiro,Tanaka, Masahiro,Arai, Masahiko
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- Synthetic approaches, functionalization and therapeutic potential of quinazoline and quinazolinone skeletons: The advances continue
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The presence of N-heterocycles as an essential structural motif in a variety of biologically active substances has stimulated the development of new strategies and technologies for their synthesis. Among the various N-heterocyclic scaffolds, quinazolines and quinazolinones form a privileged class of compounds with their diverse spectrum of therapeutic potential. The easy generation of complex molecular diversity through broadly applicable, cost-effective, practical and sustainable synthetic methods in a straightforward fashion along with the importance of these motifs in medicinal chemistry, received significant attention from researchers engaged in drug design and heterocyclic methodology development. In this perspective, the current review article is an effort to recapitulate recent developments in the eco-friendly and green procedures for the construction of highly challenging and potentially bioactive quinazoline and quinazolinone compounds in order to help medicinal chemists in designing and synthesizing novel and potent compounds for the treatment of different disorders. The key mechanistic insights for the synthesis of these heterocycles along with potential applications and manipulations of the products have also been conferred. This article also aims to highlight the promising future directions for the easy access to these frameworks in addition to the identification of more potent and specific products for numerous biological targets.
- Khan, Imtiaz,Ibrar, Aliya,Ahmed, Waqas,Saeed, Aamer
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- ZIF-8-Nanocrystalline Zirconosilicate Integrated Porous Material for the Activation and Utilization of CO2 in Insertion Reactions
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The conversion of CO2 to useful chemicals, especially to atom economical products, is the best approach to utilize an excess of CO2 present in the atmosphere. In this study, a metal-organic framework (ZIF-8) is integrated with nanocrystalline zirconosilicate zeolite to develop an integrated porous catalyst for CO2 insertion reactions. The catalyst exhibits excellent activity for the CO2 insertion reaction of epoxide to produce cyclic carbonate in neat condition without the addition of any co-catalyst. The catalyst is stable and recyclable during the cyclic carbonate synthesis. Further, the catalyst also exhibits very good activity in another CO2 insertion reaction to produce quinazoline-2,4(1H, 3H)-dione.
- Srivastava, Diksha,Rani, Poonam,Srivastava, Rajendra
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- Delineating the Mechanism of Ionic Liquids in the Synthesis of Quinazoline-2,4(1H,3H)-dione from 2-Aminobenzonitrile and CO2
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Ionic liquids (ILs) are versatile solvents and catalysts for the synthesis of quinazoline-2,4-dione from 2-aminobenzonitrile and CO2. However, the role of the IL in this reaction is poorly understood. Consequently, we investigated this reaction and showed that the IL cation does not play a significant role in the activation of the substrates, and instead plays a secondary role in controlling the physical properties of the IL. A linear relationship between the pKa of the IL anion (conjugate acid) and the reaction rate was identified with maximum catalyst efficiency observed at a pKa of >14.7 in DMSO. The base-catalyzed reaction is limited by the acidity of the quinazoline-2,4-dione product, which is deprotonated by more basic catalysts, leading to the formation of the quinazolide anion (conjugate acid pKa 14.7). Neutralization of the original catalyst and formation of the quinazolide anion catalyst leads to the observed reaction limit.
- Hulla, Martin,Chamam, Sami M. A.,Laurenczy, Gabor,Das, Shoubhik,Dyson, Paul J.
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- [TBDH][HFIP] ionic liquid catalyzed synthesis of quinazoline-2,4(1H,3H)-diones in the presence of ambient temperature and pressure
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The utilization of carbon dioxide under mild reaction conditions is an important aspect of the sustainable chemistry point of view. Herein, we prepared three bifunctional protic ionic liquids having 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) as a cation and an alcohol anions were prepared by simple neutralization of the super base TBD with proton donor alcohols such as hexafluoroisopropanol (HFIP), TFE (2,2,2-Trifluoroethanol) and TFA (2,2,2-Trifluoroacetic acid). These PILs were used as catalysts for chemical fixation of carbon dioxide into quinazoline-2,4(1H,3H)-diones. [TBDH+][HFIP-] protic ionic liquid (PIL) shows very good result compare to other PILs. As a bifunctional ionic liquid, it simultaneously activates 2-aminobenzonitrile as well as CO2 and shows excellent performance for the conversion of 2-aminobenzonitrile to quinazoline-2,4(1H,3H)-diones in presence of CO2 balloon pressure at 35 °C temperature. Moreover, the [TBDH+][HFIP-] PIL can be recycled up to six recycle run.
- Phatake, Vishal V.,Gokhale, Tejas A.,Bhanage, Bhalchandra M.
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- Design, synthesis, in silico ADMET, docking, and antiproliferative evaluations of [1,2,4]triazolo[4,3-c]quinazolines as classical DNA intercalators
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Eleven novel [1,2,4]triazolo[4,3-c]quinazolines were designed, synthesized, and evaluated against HepG2 and HCT-116 cells. The molecular design was performed to investigate the binding mode of the proposed compounds with the DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling. HCT-116 was found to be the most sensitive cell line to the influence of the new derivatives. In particular, compounds 6f and 6e were found to be the most potent derivatives over all the tested compounds against the two HepG2 and HCT116 cancer cell lines, with IC50 = 23.44 ± 2.9, 12.63 ± 1.2, and 25.80 ± 2.1, and 14.32 ± 1.5 μM, respectively. Although compounds 6f and 6e displayed less activity than doxorubicin (IC50 = 7.94 ± 0.6 and 8.07 ± 0.8 μM, respectively), both could be useful as a template for future design, optimization, and investigation to produce more potent anticancer analogs. The most active derivatives 6a, 6c, 6e, and 6f were evaluated for their DNA-binding activities. Compound 6f displayed the highest binding affinity. This compound potently intercalates DNA at a decreased IC50 value (54.08 μM). Compounds 6a, 6c, and 6e exhibited good DNA-binding affinities, with IC50 values of 79.35, 84.08, and 59.35 μM, respectively. Furthermore, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles were calculated for the four most active compounds in comparison to doxorubicin as a reference drug. Our derivatives 6a, 6c, 6e, and 6f displayed very good in-silico-predicted ADMET profiles. Doxorubicin violates three of Lipinski's rules, our derivatives 6a, 6c, 6e, and 6f do not violate any rule.
- Alesawy, Mohamed S.,Eissa, Ibrahim H.,El-Adl, Khaled,Ibrahim, Mohamed-Kamal
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- Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors
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Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 μM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 μM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.
- Abdallah, Abdallah E.,Abo-Saif, Mariam A.,Al Ward, Maged Mohammed Saleh,Alesawy, Mohamed S.,Eissa, Sally I.,El-Feky, Ola A.,El-Zahabi, Mohamed Ayman,Elkaeed, Eslam B.,Mabrouk, Reda R.,Mehany, Ahmed B. M.
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p. 573 - 591
(2022/01/20)
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- Synthesis and Anti-Proliferation Activity Evaluation of Novel 2-Chloroquinazoline as Potential EGFR-TK Inhibitors
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A novel series of 2-chloroquinazoline derivatives had been synthesized and their anti-proliferation activities against the four EGFR high-expressing cells A549, NCI-H1975, AGS and HepG2 cell lines were evaluated. The preliminary SAR study of the scaffold of new compounds showed that the compounds with a chlorine substituent on R3 had a better anti-proliferation activity than those substituted by hydrogen atom or vinyl group. Among them, 2-chloro-N-[2-chloro-4-(3-chloro-4-fluoroanilino)quinazolin-6-yl]acetamide (10b) had the best activity, and the corresponding IC50 were 3.68, 10.06, 1.73 and 2.04 μM, respectively. And compound 10b had better or equivalent activity against four cell lines than Gefitinib. The activity of the compound 10b on the EGFR enzyme was subsequently tested. The Wound Healing of A549, AGS and HepG2 cells by this compound showed that the compound can inhibit the migration of cancer cells. Finally, the action channel of the compound 10b was supported by western blotting experiments. It provides useful information for the design of EGFR-TK inhibitors.
- Jin, Hao,Rao, Guo-Wu,Xu, Xuan-Bo,Zhang, Wen,Zheng, Quan
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- Method for efficiently catalytically converting carbon dioxide into quinazoline diketone compound by using eutectic solvent under room temperature and atmospheric pressure conditions
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The invention relates to a method for efficiently catalytically converting carbon dioxide into quinazoline diketone compounds by using a deep eutectic solvent under room temperature and atmospheric pressure conditions. According to the method, the deep eutectic solvent synthesized by adopting carbon dioxide and o-aminobenzonitrile with different substituent groups as raw materials, adopting ethylene glycol as a hydrogen bond donor, and adopting 1,5-diazabicyclo[4.3.0] non-5-ene (DBN) as a hydrogen bond acceptor, with the molar ratio of the hydrogen bond donor to the hydrogen bond receptor being 1:4, 1:1 and 4:1 is adopted as a catalyst, and the quinazoline diketone compound is synthesized at room temperature under atmospheric pressure for 1-24 h with the ratio of the substrate dosage to the catalyst dosage being 0.4: 3, 0.7: 3 and 1: 3. The invention provides the method for efficiently catalytically converting carbon dioxide into quinazoline diketone compounds by using the eutectic solvent under the conditions of room temperature and atmospheric pressure, and the method is simple and convenient, high in yield, low in cost, low in energy consumption, green and environment-friendly, avoids the use of a transition metal catalyst, and has very high practical application value.
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Paragraph 0026-0031; 0036-0037
(2021/07/17)
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- Proton type ionic liquid [HDBN] [2-PyOH] and preparation and application thereof
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The invention discloses proton type ionic liquid [HDBN] [2-PyOH] and preparation and application thereof, and belongs to the technical field of catalysts. The preparation method comprises the steps that 1, 5-diazabicyclo [4.3. 0] nonyl-5-ene reacts with 2-hydroxypyridine to prepare protonic ionic liquid [HDBN] [2-PyOH]; and as a catalyst, the ionic liquid can catalyze CO2 and o-aminobenzonitrile compounds to efficiently react under mild conditions to obtain a series of quinazoline-2, 4 (1H, 3H)-diketone compounds. The proton type ionic liquid catalyst has the advantages of simple synthesis process, excellent catalytic performance, good substrate expansion capability, easy product separation and the like, and has a good industrial application prospect.
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Paragraph 0021; 0025-0049
(2021/11/21)
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- The room-temperature, ambient-pressure conversion of CO2into value-added pharmaceutical products quinazoline-2,4(1: H,3 H)-diones
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As global warming due to CO2 emissions has become a widely recognized concern, CO2 capture, sequestration, neutralization, and conversion have become possible solutions to address this concern. Among these approaches, the conversion of CO2 into fuels or value-added products has attracted considerable attention. In this work, we report the high-efficiency conversion of CO2 to important industrial raw materials for pharmaceutical compounds, quinazoline-2,4(1H,3H)-diones, via reactions with 2-aminobenzonitriles at room temperature and under ambient pressure, with high conversion yields (91.5-99.3%). 1,8-Diazabicyclo-[5.4.0]-undec-7-ene (DBU), 1,1,3,3-tetramethylguanidine (TMG), and cholinium (Ch) ammonium-based ionic liquids (ILs) are employed as catalysts during the process. Cations with a pKa value near 11.9 and anions with a pKa value range of 10 to 15 are necessary for the reaction. The experimental results indicate that the ionic liquid pair [HDBU+][3-Cl-PhO-] has high efficiency under very mild conditions, obtaining high product yields of 91.5% at 25 °C and 1 atm and 99.3% at 30 °C and 1 atm. More importantly, the catalysts retain high efficiency and activity after 5 consecutive cycles. To gain insightful understanding of the reaction, density functional theory (DFT) calculations were conducted to study the reaction mechanism. The computational results indicate that the catalytic process contains three stages: cyano activation, intramolecular rearrangement, and intramolecular cyclization. Of these, the rate-determining step is cyano activation, which shows an energy barrier of 24.5 kcal mol-1. Tuning the types of ions in ILs can effectively reduce this energy barrier and allow high efficiencies.
- Chen, Xiaobo,Feng, Xiantao,Fyffe, Phoebe,Wang, Guan,Zhang, Xihong,Zheng, Tingting,Zuo, Chunshan
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p. 21130 - 21138
(2021/10/30)
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- Ionic liquid[DBUH][BO2]: an excellent catalyst for chemical fixation of CO2under mild conditions
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The green basic IL[DBUH][BO2]was easily synthesized for the first time and used to catalyze the cycloaddition of CO2and epoxides under solvent- and halogen-free conditions at atmospheric pressure and room temperature with high target product yields. Moreover, this IL could be easily recovered and reused at least five times without activity loss. The basic anion and the cation with N-H had excellent synergistic catalytic effects on promoting these reactions. Particularly, this basic IL, the anion of which had a strong nucleophilic ability, was also very effective for the reactions of CO2and 2-aminobenzonitriles into quinazoline-2,4(1H,3H)-diones, giving the desired products in high yields at atmospheric pressure and room temperature.
- Wang, Zheng,Li, Da,Chen, Shangqing,Hu, Jiayin,Gong, Yanxi,Guo, Yafei,Deng, Tianlong
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supporting information
p. 4611 - 4616
(2021/03/22)
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- Synthesis of acyclic nucleoside phosphonates targeting flavin-dependent thymidylate synthase in Mycobacterium tuberculosis
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Flavin-Dependent Thymidylate Synthase (FDTS) encoded by ThyX gene was discovered as a new class of thymidylate synthase involved in the de novo synthesis of dTMP named only in 30 % of human pathogenic bacteria. This target was pursed for the development of new antibacterial agents against multiresistant pathogens. We have developed a new class of ANPs based on the mimic of two natural's cofactors (dUMP and FAD) as inhibitors against Mycobacterium tuberculosis ThyX. Several synthetic efforts were performed to optimize regioselective N1-alkylation, cross-coupling metathesis and Sonogashira cross-coupling. Compound 19c showed a poor 31.8% inhibitory effect on ThyX at 200 μM.
- Agrofoglio, Luigi A.,Becker, Hubert F.,Biteau, Nicolas G.,Lambry, Jean-Christophe,Myllykallio, Hannu,Roy, Vincent
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- Structure-Based Optimization of Quinazolines as Cruzain and TbrCATL Inhibitors
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The cysteine proteases, cruzain and TbrCATL (rhodesain), are therapeutic targets for Chagas disease and Human African Trypanosomiasis, respectively. Among the known inhibitors for these proteases, we have described N4-benzyl-N2-phenylquinazoline-2,4-diamine (compound 7 in the original publication, 1a in this study), as a competitive cruzain inhibitor (Ki = 1.4 μM). Here, we describe the synthesis and biological evaluation of 22 analogs of 1a, containing modifications in the quinazoline core, and in the substituents in positions 2 and 4 of this ring. The analogs demonstrate low micromolar inhibition of the target proteases and cidal activity against Trypanosoma cruzi with up to two log selectivity indices in counterscreens with myoblasts. Fourteen compounds were active against Trypanosoma brucei at low to mid micromolar concentrations. During the optimization of 1a, structure-based design and prediction of physicochemical properties were employed to maintain potency against the enzymes while removing colloidal aggregator characteristics observed for some molecules in this series.
- Barbosa Da Silva, Elany,Rocha, Débora A.,Fortes, Isadora S.,Yang, Wenqian,Monti, Ludovica,Siqueira-Neto, Jair L.,Caffrey, Conor R.,McKerrow, James,Andrade, Saulo F.,Ferreira, Rafaela S.
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p. 13054 - 13071
(2021/09/13)
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- Synthesis and enzymological characterization of some 2-(Substituted-phenylamino)quinazolin-4(3h)-one derivatives as potent α-glucosidase inhibitors in vitro
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Background: α-Glucosidase is an important hydrolytic enzyme playing a vital role in digestion of carbohydrates. It catalyzes the final step of carbohydrates digestion in biological systems and converts unabsorbed oligosaccharides and disaccharides into monosaccharides, thus resulting in hyperglycemia for diabetic patients. In this respect, it has been considered as a therapeutic target for the treatment of type 2 diabetes since the enzyme inhibition delays carbohydrate digestion and monosaccharide absorption and subsequently reduces postprandial plasma glucose levels. Objective: In this study, fourteen 2-(substitutedphenylamino)quinazolin-4(3H)-one derivatives were synthesized and evaluated for their α-glucosidase inhibitory activities. Methods: The structures of the synthesized compounds were confirmed by spectral and elemental analyses. The biological activity and enzyme inhibition kinetic studies were performed by spectro-photometrical method using microplate reader. Physicochemical and drug-likeness properties of selected compounds were predicted by in silico method. Results: The biological activity results revealed that all of the synthesized compounds showed more potent α-glucosidase inhibitory activity in the range of IC50 = 58 ± 2-375 ± 15 μM when compared to the standard drug acarbose (IC50 = 892 ± 7 μM). Among the tested compounds, compound 12 bearing chlorine substituent at ortho position on N-phenyl ring displayed the highest inhibition with an IC50 value of 58 ± 2 μM against α-glucosidase. Furthermore, the enzyme inhibition kinetic study of the most active compound 12 indicated that the compound inhibited the α-glucosidase enzyme as uncompetitive with a Ki value of 63.46 μM. On the other hand, physicochemical and drug-likeness properties of selected compounds were predicted by in silico method. According to the results, it can be speculated that synthesized 2-phenylaminoquinazolin-4(3H)-one derivatives possessed favorable drug-likeness and pharmacokinetic profiles. Conclusion: In the light of results, 2-(substitutedphenylamino)quinazolin-4(3H)-one derivatives may serve as lead compounds to develop novel α-glucosidase inhibitors.
- Ayan, Emre Kadir,Soyer, Zeynep,Uysal, ?irin
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p. 723 - 732
(2021/10/02)
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- Design and discovery of new 1,2,4-triazolo[4,3-c]quinazolines as potential DNA intercalators and topoisomerase II inhibitors
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A new series of 1,2,4-triazolo[4,3-c]quinazoline derivatives was designed and synthesized as Topo II inhibitors and DNA intercalators. The cytotoxic effect of the new members was evaluated in vitro against a group of cancer cell lines including HCT-116, HepG-2, and MCF-7. Compounds 14c, 14d, 14e, 14e, 15b, 18b, 18c, and 19b exhibited the highest activities with IC50 values ranging from 5.22 to 24.24 μM. Furthermore, Topo II inhibitory activities and DNA intercalating affinities of the most promising candidates were evaluated as a possible mechanism for the antiproliferative effect. The results of the Topo II inhibition and DNA binding tests were coherent with that of in vitro cytotoxicity. Additionally, the most promising compound 18c was analyzed in HepG-2 cells for its apoptotic effect and cell cycle arrest. It was found that 18c can induce apoptosis and arrest the cell cycle at the G2–M phase. Finally, molecular docking studies were carried out for the designed compounds against the crystal structure of the DNA?Topo II complex as a potential target to explore their binding modes. On the basis of these studies, it was hypothesized that the DNA binding and/or Topo II inhibition would participate in the noted cytotoxicity of the synthesized compounds.
- Alesawy, Mohamed S.,Al-Karmalawy, Ahmed A.,Elkaeed, Eslam B.,Alswah, Mohamed,Belal, Ahmed,Taghour, Mohammed S.,Eissa, Ibrahim H.
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- [1,2,4]Triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4′,3′-c]quinazoline derived DNA intercalators: Design, synthesis, in silico ADMET profile, molecular docking and anti-proliferative evaluation studies
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In view of their DNA intercalation activities as anticancer agents, novel fifteen [1,2,4]triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4′,3′-c]quinazoline derivatives have been designed, synthesized and evaluated against HepG2 and HCT-116. The molecular design was performed to investigate the binding mode of the proposed compounds with DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling studies. HCT-116 was found to be more sensitive cell lines to the influence of the new derivatives. In particular, compounds 16, 18, 11 and 5 were found to be the most potent derivatives with IC50 = 3.61, 6.72, 7.16 and 5.18 μM respectively against HepG2 cell line. Also, compounds 16, 18, 11 and 5 displayed IC50 = 2.85, 3.82, 4.97 and 6.40 μM respectively against HCT-116 cell line. These derivatives displayed higher activities than doxorubicin, (IC50 = 7.94 and 8.07 μM respectively) against the two HepG2 and HCT-116 cell lines. The most active anti-proliferative derivatives 5, 6, 10, 11, 13, 16, 18, 19 and 20 were further evaluated for their DNA-binding affinity which revealed the ability of these compounds to intercalate DNA. The tested compounds displayed very strong to moderate DNA-binding affinities. Compounds 16 and 18 potently intercalate DNA at IC50 values of 26.03 and 28.37 μM respectively which were lower than IC50 of Doxorubicin (IC50 = 31.27). This finding indicated that these derivatives exhibited higher DNA binding activities than Doxorubicin. Also, compounds 11 and 5 displayed very strong DNA binding at IC50 = 30.84 and 33.56 μM respectively, which were nearly equipotent to that of doxorubicin. Moreover, most of our derivatives exhibited good ADMET profile.
- El-Adl, Khaled,Ibrahim, Mohamed-Kamal,Alesawy, Mohammed S.I.,Eissa, Ibrahim H.
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- 1,2,4-Triazolo[4,3-c]quinazolines: a bioisosterism-guided approach towards the development of novel PCAF inhibitors with potential anticancer activity
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Targeting PCAF with small inhibitor molecules has emerged as a potential therapeutic strategy for the treatment of cancer. Recently, L-45 was identified as a potent triazolophthalazine inhibitor of the PCAF bromodomain. Here, we report the bioisosteric modification of the triazolophthalazine ring system of L-45 to its bioisosteric triazoloquinazoline while maintaining other essential structural fragments for effective binding with the binding site of PCAF. Consequently, a set of sixteen triazoloquinazoline derivatives were designed, synthesized, and investigated for their anticancer activity against four human cancer cell lines. Five derivatives demonstrated comparable cytotoxic activity with that of doxorubicin as a reference anticancer drug. Among them, compound23showed the most potent activity with IC50values of 6.12, 4.08, 7.17, and 6.42 μM against HePG2, MCF-7, PC3, and HCT-116, respectively. Also, compound21exhibited comparable cytotoxic effects with that of doxorubicin against the selected cancer cell lines with IC50values in the range of 7.41-9.58 μM. Molecular docking and pharmacokinetic studies were additionally performed to rationalize the binding affinities of the newly designed triazoloquinazolines toward the active site of histone acetyltransferase PCAF and to evaluate the druggability of new compounds. The results of these studies suggested that PCAF binding could be the mechanism of action of these derivatives.
- El-Shershaby, Mohamed H.,Ghiaty, Adel,Bayoumi, Ashraf H.,Ahmed, Hany E. A.,El-Zoghbi, Mona S.,El-Adl, Khaled,Abulkhair, Hamada S.
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p. 11136 - 11152
(2021/07/06)
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- From triazolophthalazines to triazoloquinazolines: A bioisosterism-guided approach toward the identification of novel PCAF inhibitors with potential anticancer activity
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Inhibition of PCAF bromodomain has been validated as a promising strategy for the treatment of cancer. In this study, we report the bioisosteric modification of the first reported potent PCAF bromodomain inhibitor, L-45 to its triazoloquinazoline bioisosteres. Accordingly, three new series of triazoloquinazoline derivatives were designed, synthesized, and assessed for their anticancer activity against a panel of four human cancer cells. Three derivatives demonstrated comparable cytotoxic activity with the reference drug doxorubicin. Among them, compound 22 showed the most potent activity with IC50 values of 15.07, 9.86, 5.75, and 10.79 μM against Hep-G2, MCF-7, PC3, and HCT-116 respectively. Also, compound 24 exhibited remarkable cytotoxicity effects against the selected cancer cell lines with IC50 values of 20.49, 12.56, 17.18, and 11.50 μM. Compounds 22 and 25 were the most potent PCAF inhibitors (IC50, 2.88 and 3.19 μM, respectively) compared with bromosporine (IC50, 2.10 μM). Follow up apoptosis induction and cell cycle analysis studies revealed that the bioisostere 22 could induce apoptotic cell death and arrest the cell cycle of PC3 at the G2/M phase. The in silico molecular docking studies were additionally performed to rationalize the PCAF inhibitory effects of new triazoloquinazoline bioisosteres.
- El-Shershaby, Mohamed H.,Ghiaty, Adel,Bayoumi, Ashraf H.,Al-Karmalawy, Ahmed A.,Husseiny, Ebtehal M.,El-Zoghbi, Mona S.,Abulkhair, Hamada S.
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- Method for preparing 2,4-(1H,3H)-quinazoline diketone compound
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The invention discloses a method for preparing a 2,4-(1H,3H)-quinazoline diketone compound. A 2-aminobenzonitrile compound as shown in a formula (1) and carbon dioxide are used as raw materials and react in 2-hydroxypyridine ionic liquid to obtain the 2,4-(1H,3H)-quinazoline diketone compound as shown in a formula (II), and the reaction formula is as shown in the specification. When the ionic liquid is applied to the reaction for preparing the 2,4-(1H,3H)-quinazoline diketone compound, the reaction condition is mild, the separation and purification process of the product is simple, the product yield is high, and the substrate application range is wide.
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Paragraph 0022-0048; 0065
(2021/05/12)
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- Discovery of quinazolinyl-containing benzamides derivatives as novel HDAC1 inhibitors with in vitro and in vivo antitumor activities
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A series of quinazolinyl-containing benzamide derivatives were designed, synthesized and evaluated for their in vitro histone deacetylase 1 (HDAC1) inhibitory activities. Compounds 11a surpassed the known class I selective HDAC inhibitor MS-275 in both HDAC1 enzymatic inhibitory activity and cellular anti-proliferative activity against a selected set of cancer cell types (Hut78, K562, Hep3B and HCT116 cells) with no observed effects on human normal cells. In particular, compound 11a inhibited HDAC1 over the other tested HDACs isoforms (HDAC2, HDAC6 and HDAC8) with acceptable safety profiles. Moreover, compound 11a displayed favorable oral pharmacokinetic properties and showed significant antitumor activity in the A549 tumor xenograft model in vivo.
- Zhang, Zixue,Zhang, Qingwei,Zhang, Hao,Jiao, Minru,Guo, Zheng,Peng, Xinyan,Fu, Lei,Li, Jianqi
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- Design, synthesis and evaluation of anti-proliferative activity of 2-aryl-4-aminoquinazoline derivatives as EGFR inhibitors
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A class of 2-aryl-4-aminoquinazoline derivatives (7a-7j, 8a-8h, 9a-9h and 10a-10k) were designed, synthesized and evaluated as EGFR inhibitors. The anti-proliferative activity of compounds in vitro showed that compound 9e was considered to be a promising derivative. Compared with the lead compound Angew2017-7634-1, 9e exhibited excellent inhibitory activity against A549, NCI-H460 and H1975 cell lines, with IC50 values of 14.33 ± 1.16 μM, 17.81 ± 1.25 μM and 13.41 ± 1.14 μM, respectively. Moreover, 9e could effectively inhibit against Ba/F3-EGFRDel19/T790M/C797S cell lines. In the kinase experiment, the most promising compound 9e exhibited excellent enzymatic inhibitory activity and selectivity for EGFRL858R/T790M, with an IC50 value of 0.74 μM. Further activity studies showed that 9e could not only induce remarkable cell-apoptosis of A549, but also block A549 cell lines in S-phase in a concentration-dependent manner. Furthermore, molecular docking study revealed the binding mode of 9e. All in all, we analyzed the structure–activity relationship of the target compounds, and explored their mechanism of action.
- Zhou, Zhihui,He, Jie,Yang, Feiyi,Pan, Qingshan,Yang, Zunhua,Zheng, Pengwu,Xu, Shan,Zhu, Wufu
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- Alcohol amine-catalyzed CO2conversion for the synthesis of quinazoline-2,4-(1H,3H)-dione in water
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The conversion of CO2to high value-added chemicals in water using environment-friendly and cost-effective catalysts is a very significant topic. In this work, a green method for the conversion of CO2catalyzed by alcohol amines has been developed. Alcohol amines showed considerable activating ability to CO2in the cyclization with 2-aminobenzonitrile to quinazoline-2,4(1H,3H)-dione in water. Notably, when diethanolamine (DEA) was used as the catalyst, 94% yield of quinazoline-2,4-(1H,3H)-dione could be achieved. A plausible mechanism has been proposed based on the1H NMR, FT-IR analysis and DFT calculation. The excellent catalytic performance is attributed to the combined effect of both the secondary amine and hydroxyl groups on alcohol amines with the assistance of water in the formation of carbamate. Water plays a bi-functional role of solvent and co-catalyst in this catalytic process. Catalysts can be easily recovered and reused five times without significant loss of activity.
- Huang, Min-Min,Sheng, Zhi-Zheng,Wu, Hai-Hong,Xia, Fei,Xue, Teng
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p. 34910 - 34915
(2020/10/12)
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- Synthesis method of 2, 4-(1H, 3H)-quinazolinedione and derivatives thereof
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The invention discloses a synthesis method of 2, 4-(1H, 3H)-quinazolinedione and derivatives thereof. CO2 and aminobenzonitrile compounds are used as raw materials, and the 2, 4-(1H, 3H)-quinazolinedione and the derivatives thereof are obtained through a reaction by adopting a catalyst as shown in the formula I provided by the invention. Reagents used in the method are cheap and easy to obtain, the product can be synthesized through a one-step method, harsh conditions of high pressure and high temperature are not needed, no metal is left in the whole reaction system, and the used catalyst canbe recycled.
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Paragraph 0067-0068
(2020/08/06)
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- DBU coupled ionic liquid-catalyzed efficient synthesis of quinazolinones from CO2 and 2-aminobenzonitriles under mild conditions
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Efficient and green strategy for the chemical conversion and fixation of CO2 is an attractive topic. In this work, we reported an efficient catalytic system of organic base coupled ionic liquids that could catalyse the synthesis of quinazolinones via cyclization of 2-aminobenzonitriles with CO2 under mild conditions (e.g., 60 °C, 0.1 MPa). It was found that 1,8-diazabicyclo[5.4.0]undec-7-ene coupled 1-butyl-3-methylimidazole acetate ionic liquids (DBU/[Bmim][OAc]) displayed excellent performance in catalysing the reactions of CO2 with 2-aminobenzonitriles, and a series of quinazolinones were obtained in high yields at atmospheric pressure. Moreover, the ILs had high stability and reusability, and can be reused at least five times without considerable decrease in catalytic activity. This protocol could also be conducted on a gram scale, and may have promising and practical applications in the production of quinazolinones.
- Bai, Qingyun,Bai, Xue,Chen, Leyuan,Gao, Xiang,Liu, Jiao,Liu, Zhaopeng,Wang, Xinlin,Zhang, Lei,Zhou, Anning,Zuo, Xin
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p. 12047 - 12052
(2020/04/10)
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- Design, synthesis and anti-influenza A virus activity of novel 2,4-disubstituted quinazoline derivatives
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Four 2,4-disubstituted quinazoline series containing various amide moieties were designed and synthesized as new anti-influenza A virus agents using the strategies of bio-isosterism and scaffold hopping. Many of them exhibit potent in vitro anti-influenza A virus activity and low cytotoxicity (CC50: >100 μM). Particularly, compounds 10a5 and 17a show better activity (IC50: 3.70–4.19 μM) and higher selective index (SI: >27.03, >23.87, respectively) against influenza A/WSN/33 virus (H1N1), opening a new direction for quinazoline derivatives in anti-influenza A virus field.
- Cen, Shan,Wang, Juxian,Wang, Minghua,Wang, Yucheng,Wang, Yujia,Zhang, Guoning,Zhu, Mei
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- Design, synthesis and in vitro anti-influenza A virus evaluation of novel quinazoline derivatives containing S-acetamide and NH-acetamide moieties at C-4
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It is an urgent need to develop more effective anti-influenza agents due to the emergence of highly pathogenic and drug-resistant influenza viruses. Herein, a series of 2,4-disubstituted quinazoline derivatives were designed, synthesized and their antiviral activities against influenza A virus were evaluated. Nine compounds (10a2, 16a, 16e, 16i, 16j, 16n, 16o, 16p and 16r) showed potent activity against influenza A virus (IAV) with IC50 at the low-micromole level (1.29–9.04 μM). Particularly, 16e and 16r possess good anti-IAV activity (IC50: 1.29 μM and 3.43 μM, respectively) and acceptable cytotoxicity, and inhibit the transcription and replication of viral RNA. Together with reasonable PK profiles of 16e, these results suggest their promising potential as candidates for further investigation.
- Zhang, Guoning,Wang, Minghua,Zhao, Jianyuan,Wang, Yujia,Zhu, Mei,Wang, Juxian,Cen, Shan,Wang, Yucheng
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- Iridium-Catalyzed C-H Amination of Weinreb Amides: A Facile Pathway toward Anilines and Quinazolin-2,4-diones
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C-H amination of arenes directed by weakly coordinating Weinreb amides has been achieved with an iridium catalyst and 2,2,2-trichloroethoxycarbonyl (Troc) azide as an aminating agent, providing a robust method of producing synthetic useful ortho-TrocNH aryl Weinreb amides. Taking advantage of the reactivity of Weinreb amide and Troc groups in the amination products, selective hydrolysis was achieved as an attractive process for the synthesis of ortho-NH2 aryl Weinreb amides, which are the building blocks useful in the synthesis of bioactive compounds, and cascade aminocyclization with primary amines was successful and provided an efficient pathway for the construction of quinazolin-2,4-diones, which are present in various alkaloids and natural products.
- Dong, Xunqing,Ma, Panpan,Zhang, Tao,Jalani, Hitesh B.,Li, Guigen,Lu, Hongjian
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p. 13096 - 13107
(2020/11/26)
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- Discovery of novel quinazolines as potential anti-tubulin agents occupying three zones of colchicine domain
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A series of novel quinazolines as tubulin inhibitors occupying three zones of colchicine domain have been designed and synthesized inspired by the recently disclosed crystal structure of verubulin analogue 6 with tubulin. Among the newly synthesized compounds, 19c showed noteworthy potency against K562, HepG2, KB, HCT-8 and MDB-MB-231 cancer cells. In vitro microtubule polymerization assays identified 19c as a potent tubulin assembly inhibitor, the binding mode of which with tubulin was confirmed by molecular modeling studies to occupy three zones of tubulin domain. Furthermore, 19c disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis and depolarized mitochondria of K562 cells. 19c also reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 19c significantly and dose dependently inhibited tumor growth in H22 liver cancer xenograft mouse model. All these results suggested that 19c deserves further research as a novel and potential anti-tubulin agent for the treatment of cancers.
- Li, Wenlong,Yin, Ying,Shuai, Wen,Xu, Feijie,Yao, Hong,Liu, Jie,Cheng, Keguang,Xu, Jinyi,Zhu, Zheying,Xu, Shengtao
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p. 380 - 390
(2018/11/10)
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- Efficient transformation of CO2 into quinazoline-2,4(1: H,3 H)-diones at room temperature catalyzed by a ZnI2/NEt3 system
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The readily available ZnI2/NEt3 system was used firstly to catalyze the transformation of CO2 and 2-aminobenzonitriles into quinazoline-2,4(1H,3H)-diones at room temperature and low CO2 pressure in high yields. Further experiments indicated that this ZnI2/NEt3 system has excellent effects on activating both amino and cyano groups.
- Chen, Shangqing,Wang, Zheng,Hu, Jiayin,Guo, Yafei,Deng, Tianlong
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p. 16164 - 16168
(2019/11/03)
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- CO2 involved synthesis of quinazoline-2,4(1 H,3 H)-diones in water using melamine as a thermoregulated catalyst
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In this study, pharmaceutically relevant quinazoline-2,4(1H,3H)-diones were synthesized eco-efficiently by cycloaddition of CO2 and 2-aminobenzonitrile in water, catalyzed by melamine as a thermoregulated catalyst. Quinazoline-2,4(1H,3H)-dione was produced selectively with 92% yield at 120 °C, 4.2 MPa, and automatically separated from the hot catalytic aqueous solution, which was reused directly for several runs until its activity decreased in an obvious manner. Then, the catalyst melamine was recrystallized from the spent aqueous solution via simple cooling and reused for another several catalytic runs. The efficient valorization of CO2 and the straightforward stepwise recovery of the products and catalyst were important to save energy and minimize process waste for the practical industrial production.
- Zhao, Guo-Ying,Mu, Ling-Ling,Ullah, Latif,Wang, Meng,Li, Hong-Ping,Guan, Xin-Xin
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p. 212 - 218
(2019/03/06)
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- BETA-ADRENERGIC RECEPTOR ALLOSTERIC MODULATORS
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Provided herein are modulators of beta-adrenergic receptors.
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Paragraph 0338; 0342; 0344
(2019/11/12)
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- Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles
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Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 μL/min/mg (human) and 33.2 μL/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 μL/min/mg; rat, 33.2 μL/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.
- Han, Sheng,Sang, Yali,Wu, Yan,Tao, Yuan,Pannecouque, Christophe,De Clercq, Erik,Zhuang, Chunlin,Chen, Fen-Er
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- Basic Salt-Lake Brine: An Efficient Catalyst for the Transformation of CO2 into Quinazoline-2,4(1 H,3 H)-diones
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The efficient transformation of CO2 into value-added chemicals with green, abundant, and cheap catalysts is an interesting and challenging topic in both green and sustainable chemistry. In this study, a series of salt-lake brines were used for the first time to catalyze the reaction of CO2 and a broad range of 2-aminobenzonitriles to form the corresponding quinazoline-2,4(1 H,3 H)-diones. It was found that the abundant, available, and inexpensive Zhabuye basic salt-lake brine could efficiently promote the reaction of 2-aminobenzonitriles under low pressure of CO2. Very high yields of value-added products were obtained. Further studies indicated that the basic carbonate and borate ions in the brine play key roles in accelerating the reactions.
- Hu, Jiayin,Chen, Shangqing,Guo, Yafei,Li, Long,Deng, Tianlong
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p. 4219 - 4225
(2018/12/11)
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- Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO2 catalyzed by tetrabutylammonium fluoride
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By employing tetrabutylammonium fluoride (TBAF) as a catalyst, the various carboxylative cyclizations of the propargylic amines having internal alkynes with CO2 proceeded to afford the corresponding 2-oxazolidinones. In this case, it was also found that the generated 2-oxazolidinones were tautomerized into the corresponding 2-oxazolones due to the basicity of TBAF. In addition, we performed the synthesis of quinazoline-2,4(1H,3H)-dione from 2-aminobenzonitrile and CO2 by using TBAF as a catalyst.
- Fujii, Akira,Matsuo, Hideaki,Choi, Jun-Chul,Fujitani, Tadahiro,Fujita, Ken-ichi
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p. 2914 - 2920
(2018/05/16)
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- CO2 transformation under mild conditions using tripolyphosphate-grafted KCC-1-NH2
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Fibrous nanosilica (KCC-1) as a catalyst support was investigated in terms of stability, recycling, and reusability. For the first time, CO2 transformation was performed via the synthesis and application of KCC-1 together with sodium tripolyphosphate (STPP) and 3-aminopropyltriethoxysilane (APTES) as its functionalized derivative. To this goal, KCC-1/STPP NPs were applied to act as a nanocatalyst with excellent catalytic activities under green reaction conditions.
- Sadeghzadeh, Seyed Mohsen,Zhiani, Rahele,Moradi, Marjan
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p. 535 - 544
(2018/04/26)
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- 3-amino nafoxidine-containing quinazoline ketone PARP (Poly Adenosine Diphosphate Ribose Polymerase)-1/2 inhibitor as well as preparation method, medicinal composition and application thereof
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The invention discloses a novel 3-amino nafoxidine-containing quinazoline-2,4(1H, 3H)-diketone PARP-1/2 (Poly Adenosine Diphosphate Ribose Polymerase) inhibitor as well as a preparation method, a medicinal composition and application thereof. Specifically, the invention relates to a 3-amino nafoxidine-containing quinazoline-2,4(1H, 3H)-diketone derivative and a medicinal salt thereof of formula (I) as shown in the specification, a preparation method thereof, a composition with one or more such compounds, preparation of the compounds, and application thereof in preparing medicines for preventing and/or treating PARP-1/2 related diseases.
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Paragraph 0240; 0241; 0242
(2018/11/22)
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- Facile and efficient synthesis of quinazoline-2,4(1H,3H)-diones through sequential hydrogenation condensation
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The heterocyclizations from various methyl (2-nitrobenzoyl)carbamates to substituted quinazoline-2,4(1H,3H)-diones under hydrogenation conditions were investigated in this study. In the presence of p-toluenesulfonic acid monohydrate in methanol, various q
- Wang, Peng-Xu,Wang, Ya-Nan,Lin, Zi-Yun,Li, Gang,Huang, Hai-Hong
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p. 1183 - 1189
(2018/04/02)
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- COMPOUND FOR ORGANIC ELECTRONIC ELEMENT, ORGANIC ELECTRONIC ELEMENT USING SAME, AND ELECTRONIC DEVICE COMPRISING SAME
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The present invention provides a novel compound capable of improving the light emitting efficiency, stability and life span of a device, and an organic electric element and an electronic device using the same.
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Paragraph 0255; 0256; 0257
(2018/09/23)
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- COMPOUND FOR ORGANIC ELECTRIC ELEMENT, ORGANIC ELECTRIC ELEMENT COMPRISING THE SAME AND ELECTRONIC DEVICE THEREOF
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The present invention provides the compound represented by Formula 1, and an organic electric element comprising a first electrode, a second electrode, and an organic material layer formed between the first electrode and the second electrode, wherein the organic material layer comprises the compound represented by Formula 1. The driving voltage of an organic electronic device can be lowered, and the luminous efficiency, color purity and life time of an organic electronic device can be improved by comprising the compound represented by Formula 1 in the organic material layer.
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Paragraph 0224; 0225; 0226
(2018/10/21)
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- Synthetic method of quinazoline-2,4(1H, 3H)-dione and derivatives thereof
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The invention discloses a synthetic method of quinazoline-2,4(1H, 3H)-dione and derivatives thereof. The method comprises the following steps: carrying out a carboxy cyclization on a substrate o-aminobenzontrile or 4,5-position substituted derivatives thereof in carbon dioxide with a diethanolamine-water solution as a catalyst, and filtering, washing and drying the obtained reaction solution to obtain the product quinazoline-2,4(1H, 3H)-dione and the derivatives thereof, wherein a molar ratio of the substrate to the diethanolamine-water solution is (3-8):(1-3); the reaction temperature of the carboxy cyclization is 60-140 DEG C, and the reaction time is 6-18 h; and the pressure of the carbon dioxide is 0.5-2 MPa. Compared with the prior art, the synthetic method has the advantages of low cost of the catalyst, high product yield and good selectivity, and is an environmentally-friendly method for homogeneous catalytic synthesis of the quinazoline-2,4(1H, 3H)-dione and the derivatives thereof.
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Paragraph 0018-0019
(2017/09/01)
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- A 2, 4 - quinazoline dione compound preparation method
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The invention belongs to the field of organic chemistry, and concretely relates to a preparation method of benzoyleneurea compounds. The preparation method comprises the following steps: a 2-aminobenzonitrile compound and carbon dioxide are used as raw materials, preferably a reaction employs acylamino divalent rare earth metal amides and DBU as catalysts at 50-150 DEG C under a normal pressure, the reaction is carried out in an aprotic polar solvent for 4-40 hours, and the benzoyleneurea compounds are obtained with a high yield. The method has the advantages of mild reaction condition, few catalyst amount, simple separation and purification, high yield and wide substrate application range.
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Paragraph 0114; 0115
(2017/10/31)
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- A amide-based bivalent rare earth metal amine compound and its preparation method and application
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The invention belongs to the field of organic chemistry, and specifically relates to amido divalent rare earth metal amide, a preparation method and applications thereof. The provided amido divalent rare earth metal amide has a novel structure. Through research, people find that amido divalent rare earth metal amide can be used as a catalyst to catalyze the reactions between 2-aminocyanobenzene and carbon dioxide to prepare 2,4-quinazoline diketone; preferably, when the mole ratio of amido divalent rare earth metal amide to 2-aminocyanobenzene is 5:100, at a temperature of 100 DEG C, under a normal pressure, and in a dimethyl sulfoxide solvent, 2,4-quinazoline diketone can be produced, and the yield can reach 12%.
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Paragraph 0063; 0064; 0065; 0066-0068; 0084; 0085-0092
(2017/08/25)
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- 5-alkyl guanidine ionic liquid, and preparation and application thereof
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The invention discloses 5-alkyl guanidine ionic liquid, and preparation and application thereof. After tetramethyl guanidine and alkyl halide are adopted to be ionized, ion exchange with metal salt is performed to prepare 5-alkyl guanidine acid radical ionic liquid, and the ionic liquid is used as a catalyst to synthesize quinazoline-2,4(1H,3H)-ketone and derivatives thereof in the carboxylation and cyclization reaction of carbon dioxide and anthranilonitrile. Compared with the prior art, the 5-alkyl guanidine ionic liquid is simple in synthetic process, low in costs and has excellent performance in a homogeneous catalysis carbon dioxide reaction process; particularly, when the 5-alkyl guanidine ionic liquid is used in the carboxylation and cyclization reaction synthesis of the carbon dioxide and the anthranilonitrile, quinazoline-2,4(1H,3H)-diketone and derivatives thereof can be obtained in a relatively mild condition; the catalytic performance is good; the reaction condition is mild; and the postprocessing is easy. Meanwhile, the 5-alkyl guanidine ionic liquid can be used as a solvent and a catalyst; the use of a large quantity of organic solvent is avoided; and the 5-alkyl guanidine ionic liquid has important significance on researching medicinal chemistry and compounds of medical intermediates.
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Paragraph 0026; 0027; 0028; 0029
(2017/07/19)
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- Cyanuric Acid-Based Organocatalyst for Utilization of Carbon Dioxide at Atmospheric Pressure
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A organocatalytic system based on economical and readily available cyanuric acid has been developed for the synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from propargylamines and 2-aminobenzonitriles under atmospheric pressure carbon dioxide. Notably, a low concentration of carbon dioxide in air was directly converted into 2-oxazolidinone in excellent yields without an external base. Through mechanistic investigation by in situ FTIR spectroscopy, cyanuric acid was demonstrated to be an efficient catalyst for carbon dioxide fixation.
- Yu, Bing,Kim, Daeun,Kim, Seoksun,Hong, Soon Hyeok
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p. 1080 - 1084
(2017/03/29)
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- Bifunctional Ionic Liquids Derived from Biorenewable Sources as Sustainable Catalysts for Fixation of Carbon Dioxide
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A series of highly efficient, bifunctional ionic liquids containing a quaternary alkyl ammonium cation and an amine anion were prepared from choline and amino acids, respectively. Nine ILs were synthesized, characterized, and applied as organocatalysts for the chemical fixation of carbon dioxide to form cyclic carbonates and quinazoline-2,4(1 H,3 H)-diones. A binary mixture of an IL and a co-catalysts generates deep eutectic solvents (DESs) and accelerates the rate of the cycloaddition reaction at atmospheric pressure and low temperature (70 °C). The presence of the hydroxyl functional group of choline and the free amine group of the amino acids in the ILs has a synergistic effect on the activation of the epoxide and carbon dioxide towards the cycloaddition reactions. These ILs are biodegradable and are synthesized from easily available biorenewable sources. Additionally, this catalytic method demonstrates ultimate environmental benignity because of the mild metal- and solvent-free conditions as well as the recyclability of the catalyst and co-catalyst.
- Saptal, Vitthal B.,Bhanage, Bhalchandra M.
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p. 1145 - 1151
(2017/03/27)
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- Discovery of novel quinazoline-2,4(1H,3H)-dione derivatives as potent PARP-2 selective inhibitors
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The PARP-2 selective inhibitor is important for clarifying specific roles of PARP-2 in the pathophysiological process and developing desired drugs with reduced off-target side effects. In this work, a series of novel quinazoline-2,4(1H,3H)-dione derivatives was designed and synthesized to explore isoform selective PARP inhibitors. As a result, compound 11a (PARP-1 IC50?=?467?nM, PARP-2 IC50?=?11.5?nM, selectivity PARP-1/PARP-2?=?40.6) was disclosed as the most selective PARP-2 inhibitor with high potency to date. The binding features of compound 11a within PARP-1 and PARP-2 were investigated respectively to provide useful insights for the further construction of new isoform selective inhibitors of PARP-1 and PARP-2 by using CDOCKER program.
- Zhao, Hailong,Ji, Ming,Cui, Guonan,Zhou, Jie,Lai, Fangfang,Chen, Xiaoguang,Xu, Bailing
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supporting information
p. 4045 - 4054
(2017/07/05)
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- Coumarins and other fused bicyclic heterocycles with selective tumor-associated carbonic anhydrase isoforms inhibitory activity
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Herein we report for the first time a series of 2-benzamido-N-(2-oxo-4-(methyl/trifluoromethyl)-2H-chromen-7-yl) benzamide 3a–f and substituted quinazolin-4(3H)-ones and 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (5, 6, 8 and 10a–c) as selective inhibitors of the tumor associated hCA IX and XII isoforms. Among the compounds reported the trifluoromethyl derivative 3d resulted the most potent against these CA isoforms with KIs of 10.9 and 6.7?nM.
- Bozdag, Murat,Alafeefy, Ahmed Mahmoud,Altamimi, Abdul Malik,Vullo, Daniela,Carta, Fabrizio,Supuran, Claudiu T.
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p. 677 - 683
(2016/12/27)
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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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- COMPOUND FOR ORGANIC ELECTRIC ELEMENT, ORGANIC ELECTRIC ELEMENT COMPRISING THE SAME AND ELECTRONIC DEVICE THEREOF
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The present invention provides: a compound having high light-emitting efficiency, having low driving voltage, and improving the lifespan of a device; an organic electric element using the same; and an electronic device thereof. The compound is represented by chemical formula 1. In the chemical formula 1, X is one of N-L^1-R^1 S, O, CR^aR^b; n and m are 0 or 1, and n+m is at least 1 (here, when n is 0, A is a single bond, and when m is 0, B is a single bond); A and B are independently one of a single bond, N-L^2-R^2, S, O, CR^cR^d; and Z^1 to Z^12 are independently CR^3, N, wherein at least one is N, and each CR^3 is independently the same or different when at least two of Z^1 to Z^12 are CR^3.(110) Substrate(120) Positive electrode(130) Hole injection layer(140) Hole transporting layer(141) Buffer layer(150) Light-emitting layer(151) Light-emitting assisting layer(160) Electron transfer layer(170) Electron injection layer(180) Negative electrodeCOPYRIGHT KIPO 2017
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Paragraph 0404-0406
(2018/02/03)
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- COMPOUND FOR ORGANIC ELECTRIC ELEMENT, ORGANIC ELECTRIC ELEMENT COMPRISING THE SAME AND ELECTRONIC DEVICE THEREOF
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The present invention refers to for high luminous efficiency, compounds capable of low driving voltage on the organic layer, the organic electric element and electronic device using the same number [...] substrate. (by machine translation)
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Paragraph 0514-0516
(2018/02/03)
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- Ionic liquid catalyst and its preparation method and application
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The invention discloses an ionic liquid catalyst as well as a preparation method and an application of the ionic liquid catalyst. The ionic liquid catalyst is composed of negative ions as shown in a formula II and any one of positive ions as shown in formulas Ia to Ic. The ionic liquid catalyst is applicable to catalyzing a reaction system in which CO2 reacts with a series of aminobenzonitrile compounds to synthesize quinazoline-2,4(1H, 3H)-diketone compounds at a normal temperature and under normal pressure; the ionic liquid catalyst is easy to synthesize, green, efficient and easy to recovery, and also has high application value. The formulas are shown in the specification.
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Paragraph 0043-0044
(2017/02/17)
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