- 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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- 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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- Ionic liquid immobilized onto fibrous nano-silica: A highly active and reusable catalyst for the synthesis of quinazoline-2,4(1 H,3 H)-diones
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In this study, a novel fibrous nano-silica (KCC-1) supported ionic liquid (KCC-1/IL) with high surface area and easy accessibility of active sites was successfully developed by a facile approach. The synthesized KCC-1/IL nanocatalyst exhibited excellent catalytic activity for the synthesis of quinazoline-2,4(1 H,3 H)-diones from CO2 and 2-aminobenzonitriles under mild conditions to the easy accessibility of the active sites. A high catalytic activity and ease of recovery from the reaction mixture by using filtration and several reuses without any significant loss in performance are additional eco-friendly attributes of this catalytic system.
- Sadeghzadeh, Seyed Mohsen
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- Application of quinazoline and pyrido[3,2-: D] pyrimidine templates to design multi-targeting agents in Alzheimer's disease
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A quinazoline and pyrido[3,2-d]pyrimidine based compound library was designed, synthesized and evaluated as multi-targeting agents aimed at Alzheimer's disease (AD). The SAR studies identified compound 8h (8-chloro-N2-isopropyl-N4-ph
- Mohamed, Tarek,Mann, Mandeep K.,Rao, Praveen P. N.
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- Amino-functionalized carbon nanofibres as an efficient metal free catalyst for the synthesis of quinazoline-2,4(1H,3H)-diones from CO2 and 2-aminobenzonitriles
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Carbon nanofibres (CNFs) functionalized with 4-amino-2,6-dimethylpyridine were found to be an efficient metal free catalyst for the synthesis of quinazoline-2,4(1H,3H)-diones from CO2 and 2-aminobenzonitriles using water as a reaction medium. The presence of water they exhibited a remarkable enhancement in reaction rates and provided high to excellent yield of the products. After completion of the reaction, the catalyst was easily separated by centrifugation and was successfully reused for several runs without showing any significant decrease in catalytic activity.
- Kumar, Subodh,Verma, Sanny,Shawat, Efrat,Nessim, Gilbert Daniel,Jain, Suman L.
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- Discovery of 2-(4-Substituted-piperidin/piperazine-1-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-quinazoline-2,4-diamines as PAK4 inhibitors with potent A549 cell proliferation, migration, and invasion inhibition activity
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A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4) inhibitors. All compounds showed significant inhibitory activity against PAK4 (half-maximal inhibitory concentration IC50 1 ?M). Among them, compounds 8d and 9c demonstrated the most potent inhibitory activity against PAK4 (IC50 = 0.060 ?M and 0.068 ?M, respectively). Furthermore, we observed that compounds 8d and 9c displayed potent antiproliferative activity against the A549 cell line and inhibited cell cycle distribution, migration, and invasion of this cell line. In addition, molecular docking analysis was performed to predict the possible binding mode of compound 8d. This series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity.
- Wu, Tianxiao,Pang, Yu,Guo, Jing,Yin, Wenbo,Zhu, Mingyue,Hao, Chenzhou,Wang, Kai,Wang, Jian,Zhao, Dongmei,Cheng, Maosheng
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- A green, facile, and one-pot synthesis of 2,4-(1H,3H)-quinazolinediones under microwave irradiations
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Quinazoline-2,4-diones are of considerable interest due to their wide pharmacological properties. Here, we have described an environmentally friendly method for the one-pot synthesis of 2,4-(1H,3H)-quinazolinediones from the reaction of anthranilic acid derivatives with urea in H2O media under microwave irradiations. This method is simple, safe, and fast which produces high yield of products without use of any catalyst. Copyright
- Nikpour, Farzad,Paibast, Touraj
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- Spidery catalyst for the synthesis of quinazoline-2,4(1H,3H)-diones
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In this study, a novel fibrous nanosilica (KCC-1) based nanocatalyst (Au, Pd, and Cu) with a high surface area and easy accessibility of active sites was successfully developed by a facile approach. KCC-1 with a high surface area was functionalized with multi-carboxylic hyperbranched polyglycerol groups (HPG) acting as robust anchors so that the metal nanoparticles (Au, Pd, and Cu) were well-dispersed on the fibers of the KCC-1 microspheres without aggregation. Because of the amplification effect of HPG, high loading capacities of the nanocatalysts were achieved. The synthesized KCC-1/HPG/X nanocatalyst exhibited excellent catalytic activity for the synthesis of quinazoline-2,4(1H,3H)-diones from CO2 and 2-aminobenzonitrile under mild conditions due to the easy accessibility of the active sites. High catalytic activity and ease of recovery from the reaction mixture by using filtration after several reuses without any significant loss of performance are additional eco-friendly attributes of this catalytic system.
- Sadeghzadeh, Seyed Mohsen
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- Alkali metal cations control over nucleophilic substitutions on aromatic fused pyrimidine-2,4-[1H,3H]-diones: Towards new PNA monomers
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In this paper we report synthesis of a series of aromatic fused pyrimidine-2,4(3H)-dione-1-yl acetic acid and new PNA monomers containing these polycyclic nucleobase analogues. Introduction of a fused aromatic ring onto the 5,6-positions of the pyrimidine-2,4-[1H,3H]-diones brings about the steric effects and the charge delocalization, both weakening the nucleophilic substitutions on the 1- and 3-positions. We found that alkali metal cations play an important role in this alkylation reaction. LiOH brings out a much more efficient alkylation than NaOH does, while KOH nearly does not work on this reaction. Such influences from the alkali metal cations are probably due to that the charge-pairing interactions between the pyrimidine-2,4-dioxide anions and the alkali metal cations rearrange the charge distribution around the whole aromatic system and increase the negative charge distribution on the 1- and 3-nitrogen atoms, which then strengthens the nucleophilic reactivity on these positions.
- Li, Pengfa,Zhan, Chuanlang,Zhang, Shanlin,Ding, Xunlei,Guo, Fengqi,He, Shenggui,Yao, Jiannian
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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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- 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; 0025-0029; 0055-0059
(2021/11/21)
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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 0071-0074
(2020/08/06)
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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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- 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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- PIPERAZINE DERIVATIVES AS MAGL INHIBITORS
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The invention provides new heterocyclic compounds having general Formula (I), or a pharmaceutically acceptable salt thereof, wherein R1, R2, X, Y1 and Y2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
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Page/Page column 219
(2019/05/02)
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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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- 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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- 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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- Pyrimidine derivatives, preparation method therefor and application of pyrimidine derivatives
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The invention belongs to the field of drug synthesis and relates to novel pyrimidine derivatives, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, preparation methods of thenovel pyrimidine derivatives and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof and use of the novel pyrimidine derivatives and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof in preparation of therapeutic agents, particularly PAK inhibitors. The derivatives disclosed by the invention are represented by a general formula (I) or (II), wherein each substituent is as defined in claims.
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Paragraph 0135; 0136; 0137; 0138
(2018/03/26)
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- Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors
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Herein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold. Based on the shape and chemical composition of the ATP-binding pocket of PAKs, we chose a 2,4-diaminoquinazoline series of inhibitors as a starting point. Guided by X-ray crystallography and a structure-based drug design (SBDD) approach, a series of novel 4-aminoquinazoline-2-carboxamide PAK4 inhibitors were designed and synthesized. The inhibitors' selectivity, therapeutic potency, and pharmaceutical properties were optimized. One of the best compounds, 31 (CZh226), showed remarkable PAK4 selectivity (346-fold vs PAK1) and favorable kinase selectivity profile. Moreover, this compound potently inhibited the migration and invasion of A549 tumor cells by regulating the PAK4-directed downstream signaling pathways in vitro. Taken together, these data support the further development of 31 as a lead compound for PAK4-targeted anticancer drug discovery and as a valuable research probe for the further biological investigation of group II PAKs.
- Hao, Chenzhou,Zhao, Fan,Song, Hongyan,Guo, Jing,Li, Xiaodong,Jiang, Xiaolin,Huan, Ran,Song, Shuai,Zhang, Qiaoling,Wang, Ruifeng,Wang, Kai,Pang, Yu,Liu, Tongchao,Lu, Tianqi,Huang, Wanxu,Wang, Jian,Lin, Bin,He, Zhonggui,Li, Haitao,Li, Feng,Zhao, Dongmei,Cheng, Maosheng
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p. 265 - 285
(2018/02/10)
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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 0022-0023
(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 0126; 0127
(2017/10/31)
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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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- SUBSTITUTED QUINAZOLINE COMPOUNDS AND PREPARATION AND USES THEREOF
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The present invention relates quinazolinone compounds of Formula (I), as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses; wherein the compounds or pharmaceutical compositions disclosed herein can be used for antagonizing the orexin receptor. The present invention also relates to uses of the compounds or pharmaceutical compositions in treating or preventing neurological and psychiatric disorders and diseases of the central nervous system in mammals, especially in humans.
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Page/Page column 52; 57
(2017/03/08)
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- OCTAHYDROPYRROLO [3, 4-c] PYRROLE DERIVATIVES AND USES THEREOF
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The invention relates to octahydropyrrolo [3, 4-c] pyrrole derivatives and uses thereof. Compounds and pharmaceutical compositions comprising the compounds provided herein are used for antagonizing orexin receptors. The invention also relates to processes for preparing the compounds and pharmaceutical compositions, and uses thereof in treating or preventing a disease related to orexin receptors.
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Paragraph 00213; 00219
(2017/07/04)
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- Azole-Anion-Based Aprotic Ionic Liquids: Functional Solvents for Atmospheric CO2 Transformation into Various Heterocyclic Compounds
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The chemical transformation of atmospheric CO2 is of great significance yet still poses a great challenge. Herein, azole-anion-based aprotic ionic liquids (ILs) were synthesized by the deprotonation of weak proton donors (e.g., 2-methylimidazole, 4-methylimidazole, and 2,4-dimethylimidazole) with tetrabutylphosphonium hydroxide, [Bu4P][OH]. We found that these ILs, such as [Bu4P][2-MIm], could activate atmospheric CO2 through the formation of carbamates. The resultant carbamate intermediates could further react with various types of substrate, including propargylic alcohols, 2-aminobenzonitriles, ortho-phenylenediamines, and 2-aminothiophenol, thereby producing α-alkylidene cyclic carbonates, quinazoline-2,4(1 H,3 H)-diones, benzimidazolones, and benzothiazoline, respectively, in moderate-to-good yields. Thus, we have achieved the transformation of CO2 at atmospheric pressure, and we expect this method to open up new routes for the synthesis of various oxygen-containing heterocyclic compounds under metal-free conditions.
- Zhao, Yanfei,Wu, Yunyan,Yuan, Guangfeng,Hao, Leiduan,Gao, Xiang,Yang, Zhenzhen,Yu, Bo,Zhang, Hongye,Liu, Zhimin
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p. 2735 - 2740
(2016/10/11)
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- Synthesis and Characterization of Amidato Divalent Lanthanide Complexes and Their Use in Forming 2,4-Quinazolidinones from CO2 and 2-Aminobenzonitriles
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Four amidato divalent lanthanide complexes, {LnLn[N(TMS)2]THF}2 [n = 1, Ln = Eu (1); n = 2, Ln = Eu (3), Yb (4); HL1 = tBuC6H4CONHC6H3(iPr)2; HL2 = C6H5CONHC6H3(iPr)2] and {L3Eu[N(TMS)2]THF}{L32Eu(THF)2} (2) [HL3 = ClC6H4CONHC6H3(iPr)2], were synthesized and extensively characterized. This is the first time that the amidato lanthanide amides 1-4 were used to catalyze the reactions of CO2 and 2-aminobenzonitriles to form quinazoline-2,4(1H,3H)-diones at atmospheric pressure. All the complexes efficiently catalyzed the transformation, with complex 3 showing the highest activity. This catalytic system gave good to excellent yields, and good functional group tolerance. Preliminary studies were conducted to investigate the reaction mechanism.
- Wang, Qianyu,Lu, Chengrong,Zhao, Bei,Yao, Yingming
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p. 2555 - 2559
(2016/06/01)
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- Bifunctional Ionic Liquids for the Multitask Fixation of Carbon Dioxide into Valuable Chemicals
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A series of task-specific ionic liquids (ILs) such as mono-, dicationic, and polymer-supported ILs were synthesized. These ILs were applied as multitasking organocatalysts for transformations of carbon dioxide into valuable chemicals through a range of reactions, including (i) cycloaddition reactions of CO2/CS2 with epoxides to form cyclic carbonates and 1,3-oxathiolane-2-thiones, (ii) transesterification of cyclic carbonates with methanol to form dimethyl carbonate, and (iii) synthesis of quinazoline-2,4(1 H,3 H)-diones and quinazoline-2,4(1 H,3 H)-dithiones from 2-aminobenzonitriles and CO2/CS2. The developed methodology is transition-metal free, solvent free, and additive free. Remarkably, the developed ILs were recyclable in up to seven consecutive cycles; thus, making this protocol green and cost effective.
- Saptal, Vitthal B.,Bhanage, Bhalchandra M.
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p. 244 - 250
(2016/01/26)
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- La-Mg mixed oxide as a highly basic water resistant catalyst for utilization of CO2 in the synthesis of quinazoline-2,4(1H,3H)-dione
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The synthesis of quinazoline-2,4(1H,3H)-dione was done by direct utilization of CO2 in the cyclization of 2-aminobenzonitrile (2-ABN) using lanthanum magnesia mixed oxide (La-Mg MO) as a strong basic catalyst under mild reaction conditions in water. It gave a conversion of ~92% with 100% selectivity at 140 °C in 14 h. La-Mg MO was prepared by hydrothermal method using urea as homogeneous precipitating agent. The catalyst was characterized by different analytical techniques like BET, XRD, FT-IR, SEM, and TGA, and the basicity by CO2-TPD and acidity by NH3 TPD. Various reaction parameters were studied to predict the reaction mechanism and kinetics. The reaction follows the Langmuir-Hinshelwood-Hougen-Watson (LHHW) type kinetics model with an apparent activation energy of 23.3 kcal mol-1. The catalyst was recycled three times with an insignificant change in activity. The overall process is clean and green.
- Rasal,Yadav, Ganapati D.
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p. 111079 - 111089
(2016/12/03)
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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 0044; 0076-0077
(2017/02/17)
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- Octahydropyrrole[3, 4-c]pyrrole derivative and using method and application thereof
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The invention relates to an ctahydropyrrole[3, 4-c]pyrrole derivative and a using method and application thereof. A compound and a drug composition containing the same are used for resisting orexin receptors. The invention further relates to methods of pr
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Paragraph 0182; 0253; 0255; 0256
(2018/02/04)
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- Carbon Dioxide Mediated Novel Synthesis of Quinazoline-2,4(1H,3H)-dione in Water
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A novel, efficient, and scalable CO2 mediated synthesis of quinazoline-2,4(1H,3H)-dione was developed by a simple cyclization of 2-aminobenzonitrile with DMF in water as the solvent. This is the first report of its kind. DMF was used as the necessary carbon source in the synthesis of quinazoline-2,4(1H,3H)-dione. This synthetic protocol is very efficient; it gives >99% conversion with excellent selectivity. The product was isolated by filtration because of the highly insoluble nature of quinazoline-2,4(1H,3H)-dione in water. The co-product, dimethyl amine, also has industrial importance, and the CO2 that is used can be recycled. This protocol has wide-spread applications in the syntheses of benzimidazole and benzothiazole.
- Rasal, Kalidas B.,Yadav, Ganapati D.
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p. 2067 - 2073
(2016/12/24)
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- Discovery of 2-aryloxy-4-amino-quinazoline derivatives as novel protease-activated receptor 2 (PAR2) antagonists
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Protease-activated receptor 2 (PAR2) is a member of G protein-coupled receptor and its activation initiates diverse inflammatory responses. Recent studies suggest that antagonists of PAR2 may provide a novel therapeutic strategy for inflammatory diseases. In this study, we have developed a series of 2-aryloxy-4-amino-quinazoline derivatives as PAR2 antagonists and examined their effects against LPS-induced inflammatory responses in RAW 264.7 macrophages. Among these derivatives, compound 2f displayed the greatest antagonistic activity with the IC50 value of 2.8 μM. Binding modes of the newly identified PAR2 antagonists were analyzed by molecular docking using IFD/MM-GBSA methods in the putative binding site of PAR2 homology model. Moreover, 2f demonstrated significant inhibitory effects on the LPS-activated pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) through the regulation of various intracellular signaling pathways involving nuclear factor-κB (NF-κB), activator protein 1 (AP-1) and the mitogen-activated protein kinases (MAPK). Furthermore, administration of 2f significantly reduced the mortality of LPS-induced sepsis in mice. These results provide useful insights into the development of novel PAR2 antagonists with anti-inflammatory activity in vitro and in vivo.
- Cho, Nam-Chul,Cha, Ji Hyoun,Kim, Hyojin,Kwak, Jinsook,Kim, Dohee,Seo, Seung-Hwan,Shin, Ji-Sun,Kim, Taehun,Park, Ki Duk,Lee, Jiyoun,No, Kyoung Tai,Kim, Yun Kyung,Lee, Kyung-Tae,Pae, Ae Nim
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p. 7717 - 7727
(2015/12/20)
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- Synthesis and antimicrobial activity of amino linked heterocycles
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Amino-linked benzoxazolyl/benzothiazolyl/benzimidazolyl quinazolines were prepared and their antimicrobial activity studied. The nitro-substituted benzothiazolyl quinazoline (8f) may be a potential antibacterial agent against Staphylococcus aureus and nitro-substituted benzimidazolyl quinazoline (9f) may be a potential antifungal agent against Aspergillus niger.
- Mallikarjuna Reddy, Lingaladinne,Dinneswara Reddy, Guda,Padmaja, Adivireddy,Padmavathi, Venkatapuram
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- Efficient synthesis of quinazoline-2,4(1H,3H)-diones from CO2 catalyzed by N-heterocyclic carbene at atmospheric pressure
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Under atmospheric pressure, quinazoline-2,4(1H,3H)-diones were obtained from the reaction of 2-aminobenzonitriles with carbon dioxide (0.1 MPa) with a catalytic amount of N-heterocyclic carbene in DMSO. It was found that various electron-donating and electron-withdrawing groups such as -OMe, -F, -Cl, -Br, -CH3, -CF3 and -CN were well tolerated to give the products in almost quantitative yields.
- Xiao, Yunqing,Kong, Xianqiang,Xu, Zhicheng,Cao, Changsheng,Pang, Guangsheng,Shi, Yanhui
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p. 5032 - 5037
(2015/03/03)
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- Tetra-butylphosphonium arginine-based ionic liquid-promoted cyclization of 2-aminobenzonitrile with carbon dioxide
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An easily prepared amino acid ionic liquid (AAIL) i.e. [TBP][Arg] comprising a tetra-butylphosphonium cation and an arginine anion was found to be an efficient and recyclable catalyst for the synthesis of quinazoline-2,4(1H,3H)-diones from 2-aminobenzonitriles and CO2 under solvent-free conditions. As a result, various 2-aminobenzonitriles bearing electron-withdrawing or electron-donating substituents worked well to afford quinazoline-2,4(1H,3H)-diones in excellent yields. Notably, this type of AAIL showed good stability, and could be easily recovered and reused five times without significant loss of its catalytic activity. This process represents an alternative approach for greener chemical fixation of CO2 to afford valuable compounds. This journal is
- Lang, Xian-Dong,Zhang, Shuai,Song, Qing-Wen,He, Liang-Nian
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p. 15668 - 15673
(2015/02/19)
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- Antileishmanial activity of a series of N2, N 4-disubstituted quinazoline-2,4-diamines
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A series of N2,N4-disubstituted quinazoline-2,4- diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure-activity and structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg-1 day-1 for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N2,N 4-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.
- Van Horn, Kurt S.,Zhu, Xiaohua,Pandharkar, Trupti,Yang, Sihyung,Vesely, Brian,Vanaerschot, Manu,Dujardin, Jean-Claude,Rijal, Suman,Kyle, Dennis E.,Wang, Michael Zhuo,Werbovetz, Karl A.,Manetsch, Roman
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p. 5141 - 5156
(2014/07/08)
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- A highly efficient way to capture CX2 (O, S) mildly in reusable ReILs at atmospheric pressure
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The highly efficient transformation of CX2 (O, S) into valuable chemicals at atmospheric pressure is an attractive topic. A novel method of preparing quinazoline derivatives by capturing CX2 (O, S) in reusable, room-temperature, reversible ionic liquids (ReILs) with high yields (up to 98%) at 40 °C and atmospheric pressure was developed in this paper. The different reaction conditions were optimized and the products were easily separated from the ReILs which could be reused at least six times without considerable loss in yield. The plausible mechanism of capturing CX2 (O, S) in the ReILs was proposed and it provides a green, efficient protocol to capture CX2 (O, S) in ReILs to synthesize quinazoline derivatives. This journal is the Partner Organisations 2014.
- Zheng, Hui,Cao, Xianting,Du, Kui,Xu, Jun,Zhang, Pengfei
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p. 3142 - 3148
(2014/06/10)
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- A protic ionic liquid catalyzes CO2 conversion at atmospheric pressure and room temperature: Synthesis of quinazoline-2,4(1H,3H)-diones
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The chemical fixation of CO2 under mild reaction conditions is of significance from a sustainable chemistry viewpoint. Herein a CO 2-reactive protic ionic liquid (PIL), [HDBU+][TFE -], was designed by neutralization of the superbase 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with a weak proton donor trifluoroethanol (TFE). As a bifunctional catalyst for simultaneously activating CO2 and the substrate, this PIL displayed excellent performance in catalyzing the reactions of CO2 with 2-aminobenzonitriles at atmospheric pressure and room temperature, thus producing a series of quinazoline-2,4(1H,3H)-diones in excellent yields. No pressure: The reaction of CO2 with various 2-aminobenzonitriles was achieved at atmospheric pressure and room temperature by using the bifunctional protic ionic liquid [HDBU+][TFE-], thus producing the title compounds in excellent yields. The ionic liquid serves as both the catalyst and solvent, and activates both CO2 and the substrates simultaneously. DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, TFE=trifluoroethanol.
- Zhao, Yanfei,Yu, Bo,Yang, Zhenzhen,Zhang, Hongye,Hao, Leiduan,Gao, Xiang,Liu, Zhimin
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supporting information
p. 5922 - 5925
(2014/06/10)
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- Efficient synthesis of quinazoline-2,4(1H,3H)-diones from CO2 using ionic liquids as a dual solvent-catalyst at atmospheric pressure
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The highly efficient transformation of CO2 into value-added chemicals is an interesting topic in green chemistry. In this work, we studied the synthesis of quinazoline-2,4(1H,3H)-diones from CO2 and 2-aminobenzonitriles in a series of ionic liquids (ILs). It was found that 1-butyl-3-methylimidazolium acetate ([Bmim]Ac), a simple and easily prepared IL, could act as both solvent and catalyst, the reactions could be carried out very efficiently at atmospheric pressure of CO2, and a high yield of the products was obtained. Further study indicated that the IL was also very efficient for converting other 2-aminobenzonitriles into their corresponding quinazoline-2,4(1H,3H)-diones in high yields at atmospheric pressure. Moreover, the separation of the products from the IL was very easy, and the IL could be reused at least five times without considerable loss in catalytic activity.
- Lu, Wenjing,Ma, Jun,Hu, Jiayin,Song, Jinliang,Zhang, Zhaofu,Yang, Guanying,Han, Buxing
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p. 221 - 225
(2014/01/06)
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- Choline hydroxide promoted chemical fixation of CO2 to quinazoline-2,4(1H,3H)-diones in water
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The efficient conversion of CO2 to high value-added chemicals in water with cheap and non-toxic catalysts is a very attractive topic in green chemistry. In this work, the transformation of CO2 and 2-aminobenzonitriles to quinazoline-2,4(1H,3H)-diones in water promoted by choline hydroxide has been studied. The effect of temperature, pressure, reaction time, and amount of catalyst on the reaction were investigated and the reaction conditions were optimized. It was demonstrated that choline hydroxide showed supernormal catalytic activity to promote this reaction as a biodegradable, environmentally friendly, green and cheap material showed supernormal catalytic activity to promote this reaction. Furthermore, the reaction mechanism was discussed.
- Lu, Wenjing,Ma, Jun,Hu, Jiayin,Zhang, Zhaofu,Wu, Congyi,Han, Buxing
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p. 50993 - 50997
(2014/12/10)
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- Amine functionalized MCM-41: An efficient heterogeneous recyclable catalyst for the synthesis of quinazoline-2,4(1H,3H)-diones from carbon dioxide and 2-aminobenzonitriles in water
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A simple covalently linked amine functionalized MCM-41 compound was investigated using mesoporous catalytic protocols as a highly efficient, heterogeneous and recyclable catalyst for the synthesis of a wide variety of quinazoline-2,4(1H,3H)-dione derivatives from 2-aminobenzonitriles and carbon dioxide in aqueous reaction medium. This catalytic system represents a heterogeneous and environmentally benign protocol. The effect of various reaction parameters, such as the influences of solvent, temperature, CO 2 pressure, and time for the synthesis of quinazoline-2,4(1H,3H)- diones were studied. The developed protocol can be applied for the synthesis of the most important key intermediate 6,7-dimethoxyquinazoline-2,4(1H,3H)-dione and several biologically active derivatives such as Prazosin, Bunazosin and Doxazosin. Besides this, the developed catalyst could be reused for five consecutive recycles without any significant loss in its catalytic activity. The amine functionalized MCM-41 catalyst was characterized by various characterization techniques such as FT-IR, TGA/DTA, XRD, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and solid state 29Si CP MAS NMR analysis. This journal is the Partner Organisations 2014.
- Nale, Deepak B.,Rana, Surjyakanta,Parida, Kulamani,Bhanage, Bhalchandra M.
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p. 1608 - 1614
(2014/06/09)
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- Efficient synthesis of quinazoline-2,4(1H,3H)-diones from CO2 and 2-aminobenzonitriles in water without any catalyst
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We discovered that the synthesis of quinazoline-2,4(1H,3H)-diones from CO2 and 2-aminobenzonitriles could proceed efficiently in water without any catalyst and excellent yields were obtained, while the reaction did not occur in organic solvents
- Ma, Jun,Han, Buxing,Song, Jinliang,Hu, Jiayin,Lu, Wenjing,Yang, Dezhong,Zhang, Zhaofu,Jiang, Tao,Hou, Minqiang
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p. 1485 - 1489
(2013/09/24)
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- Condensation reaction of ethyl 4-oxo-4h-benzo[d][1,3]-oxazine-2- carboxylates with potassium cyanate: 2,4(1H,3H)-quinazolinediones synthesis
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The condensation reaction of ethyl 4-oxo-4H-benzo[d][1,3]oxazine-2- carboxylates with acidic solution of potassium cyanate offers a novel and expedient route to the synthesis of 2,4(1H,3H)-quinazolinediones under mild reaction conditions..
- Nikpour, Farzad,Havasi, Forugh,Arzegar, Zeinab
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p. 2745 - 2748,4
(2020/09/16)
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- A facile and convenient approach for the one-pot synthesis of 2,4(1H,3H)-quinazolinediones
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A fast and efficient method is described for the one-pot synthesis of 2,4(1H,3H)-quinazolinediones by cyclization reaction of anthranilic acid derivatives with potassium cyanate and acetic acid in PEG. Good to high yields of the products obtain in short reaction times with simple work-up.
- Sharafi-Kolkeshvandi, Mahnaz,Nikpour, Farzad
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experimental part
p. 431 - 433
(2012/06/18)
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- Is CO2 fixation promoted through the formation of DBU bicarbonate salt?
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The bicyclic amidines, 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) and 1,5-diazabicyclo[4.3.0] non-5-ene (DBN), were used for the chemical fixation of carbon dioxide. The promotion for CO2 fixation is often reported through the formation of a thermally unstable DBU or DBN bicarbonate salt. To examine the effects of the DBU or DBN bicarbonate salt, reactions of 2-aminobenzonitrile with the DBU salt or DBN salt in dimethylformamide (DMF) were performed at 20°C for 24 h in argon or carbon dioxide (0.1 MPa). However, in all the cases, 1H-quinazoline-2,4-dione was not obtained completely. In contrast with room temperature reactions, 2-aminobenzonitriles and DBU bicarbonate salt in DMF reacted for 4 h under high temperature (80°C) and CO2 atmosphere (0.1 MPa) gave 1H-quinazoline-2,4-diones in good to excellent yields. At high-temperature conditions, DBU bicarbonate salt is decomposed to DBU and carbon dioxide. Also, the carbonylation of 2-aminobenzonitrile using DBU and carbon dioxide afforded 1H-quinazoline-2,4- dione in good yields under similar reaction conditions. These results suggest that the combination of DBU or DBN as a strong base and carbon dioxide is much more important than the in situ formation of DBU or DBN bicarbonate salt for the acceleration of CO2 fixation.
- Mizuno, Takumi,Nakai, Takeo,Mihara, Masatoshi
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experimental part
p. 276 - 280
(2012/07/28)
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- A bifunctional tungstate catalyst for chemical fixation of CO2 at atmospheric pressure
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No pressure: A simple monomeric tungstate, [WO4]2-, serves as a highly efficient homogeneous catalyst for various transformations of CO2 at atmospheric pressure. The tungsten-oxo moiety activates CO2 and the substrate simultaneously. The catalyst system is high yielding and applicable to a wide range of substrates such as amines (see scheme), 2-aminobenzonitriles, and propargylic alcohols. Copyright
- Kimura, Toshihiro,Kamata, Keigo,Mizuno, Noritaka
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supporting information; experimental part
p. 6700 - 6703
(2012/08/28)
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- Efficient [WO4]2--catalyzed chemical fixation of carbon dioxide with 2-aminobenzonitriles to quinazoline-2,4(1 H,3 H)-diones
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A simple monomeric tungstate, TBA2[WO4] (I, TBA = tetra-n-butylammonium), could act as an efficient homogeneous catalyst for chemical fixation of CO2 with 2-aminobenzonitriles to quinazoline-2,4(1H,3H)-diones. Various kinds of structurally diverse 2-aminobenzonitriles could be converted into the corresponding quinazoline-2,4(1H,3H)-diones in high yields at atmospheric pressure of CO 2. Reactions of inactive 2-amino-4-chlorobenzonitrile and 2-amino-5-nitrobenzonitrile at 2 MPa of CO2 also selectively proceeded. The present system was applicable to a g-scale reaction of 2-amino-5-fluorobenzonitrile (10 mmol scale) with CO2 and 1.69 g of analytically pure quinazoline-2,4(1H,3H)-dione could be isolated. In this case, the turnover number reached up to 938 and the value was the highest among those reported for base-mediated systems so far. NMR spectroscopies showed formation of the corresponding carbamic acid through the simultaneous activation of both 2-aminobenzonitirile and CO2 by I. Kinetic and computational studies revealed that I plays an important role in conversion of the carbamic acid into the product.
- Kimura, Toshihiro,Sunaba, Hanako,Kamata, Keigo,Mizuno, Noritaka
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p. 13001 - 13008
(2013/02/22)
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- HETEROCYCLIC INHIBITORS OF HISTAMINE RECEPTORS FOR THE TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as inhibitors of H1R and/or H4R for the treatment or prevention of inflammatory, autoimmune, allergic, and ocular diseases.
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Page/Page column 79
(2011/10/05)
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