13794-72-4Relevant academic research and scientific papers
Novel 3,4-dihydro-4-oxoquinazoline-based acetohydrazides: Design, synthesis and evaluation of antitumor cytotoxicity and caspase activation activity
Huan, Le Cong,Tran, Phuong-Thao,Phuong, Cao Viet,Duc, Phan Huy,Anh, Duong Tien,Hai, Pham The,Huong, Le Thi Thu,Thuan, Nguyen Thi,Lee, Hye Jin,Park, Eun Jae,Kang, Jong Soon,Linh, Nguyen Phuong,Hieu, Tran Trung,Oanh, Dao Thi Kim,Han, Sang-Bae,Nam, Nguyen-Hai
, (2019)
In search for novel small molecules with antitumor cytotoxicity via activating procaspase-3, we have designed and synthesized three series of novel (E)-N′-benzylidene-4-oxoquinazolin-3(4H)-yl)acetohydrazides (5a-j, 6a-h, and 7a-h). On the phenyl ring ò the benzylidene part, three different substituents, including 2-OH-4-OCH3, 4-OCH3, and 4-N(CH3)2, were introduced, respectively. Biological evaluation showed that the acetohydrazides in series 5a-j, in which the phenyl ring of the benzylidene part was substituted by 2-OH-4-OCH3 substituent, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). Most of the compounds, in this series, especially compounds 5c, 5b and 5h, also significantly activated caspase-3 activity. Among these, compound 5c displayed 1.61-fold more potent than PAC-1 as caspase-3 activator. Cell cycle analysis showed that compounds 5b, 5c, and 5h significantly arrested the cell cycle in G1 phase. Further apoptotic studies also demonstrated compounds 5b, 5c, and 5h as strong apoptotic cell death inducers. The docking simulation studies showed that these compounds could activate procaspase via chelating Zn2+ ion bound to the allosteric site of the zymogen.
Di-6R,7R1-4(3H)-oxo-2-quinazolinyl-substituted cyclobutanes from pinic and sym-homopinic acids
Avotin'sh,Petrova,Strakovs
, p. 817 - 821 (2002)
The corresponding diamides were obtained from reaction of cis-3-carboxy-2,2-dimethylcyclobutylacetic acid (pinic acid) and of cis/trans-3-(carboxymethy)-2,2-dimethylcyclobutyl-acetic acid (homopinic acid) dichlorides with two equivalents of 5-bromo-, 4-chloro-, and 4,5-dimethoxyanthranilic acids. Treatment of them with formamide leads to the formation of the corresponding 2,2-dimethyl-3-[4(3H)-oxo-2-quinazolinyl]methyl-1-[4(3H)-oxo-2-quinazolinyl] cyclobutanes and 2,2-dimethyl-1,3-di[4(3H)-oxo-2-quinazolinylmethyl] cyclobutanes.
Cobalt-Catalyzed Tandem Transformation of 2-Aminobenzonitriles to Quinazolinones Using Hydration and Dehydrogenative Coupling Strategy
Samim, Sk. Abdus,Roy, Bivas Chandra,Nayak, Sourav,Kundu, Sabuj
, p. 11359 - 11367 (2020)
A tandem synthesis of quinazolinones from 2-aminobenzonitriles is demonstrated here by using an aliphatic alcohol-water system. For this transformation, a cheap and easily available cobalt salt and P(CH2CH2PPh2)3 (PP3) ligand were employed. The substrate scope, scalability, and synthesis of natural products exhibited the vitality of this protocol.
Synthesis, biological evaluation and molecular docking studies of novel 1,2,3-triazole-quinazolines as antiproliferative agents displaying ERK inhibitory activity
Nunes, Paulo Sérgio Gon?alves,da Silva, Gabriel,Nascimento, Sofia,Mantoani, Susimaire Pedersoli,de Andrade, Peterson,Bernardes, Emerson Soares,Kawano, Daniel Fábio,Leopoldino, Andreia Machado,Carvalho, Ivone
, (2021)
ERK1/2 inhibitors have attracted special attention concerning the ability of circumventing cases of innate or log-term acquired resistance to RAF and MEK kinase inhibitors. Based on the 4-aminoquinazoline pharmacophore of kinases, herein we describe the synthesis of 4-aminoquinazoline derivatives bearing a 1,2,3-triazole stable core to bridge different aromatic and heterocyclic rings using copper-catalysed azide-alkyne cycloaddition reaction (CuAAC) as a Click Chemistry strategy. The initial screening of twelve derivatives in tumoral cells (CAL-27, HN13, HGC-27, and BT-20) revealed that the most active in BT-20 cells (25a, IC50 24.6 μM and a SI of 3.25) contains a more polar side chain (sulfone). Furthermore, compound 25a promoted a significant release of lactate dehydrogenase (LDH), suggesting the induction of cell death by necrosis. In addition, this compound induced G0/G1 stalling in BT-20 cells, which was accompanied by a decrease in the S phase. Western blot analysis of the levels of p-STAT3, p-ERK, PARP, p53 and cleaved caspase-3 revealed p-ERK1/2 and p-STA3 were drastically decreased in BT-20 cells under 25a incubation, suggesting the involvement of these two kinases in the mechanisms underlying 25a-induced cell cycle arrest, besides loss of proliferation and viability of the breast cancer cell. Molecular docking simulations using the ERK-ulixertinib crystallographic complex showed compound 25a could potentially compete with ATP for binding to ERK in a slightly higher affinity than the reference ERK1/2 inhibitor. Further in silico analyses showed comparable toxicity and pharmacokinetic profiles for compound 25a in relation to ulixertinib.
Commercial Copper-Catalyzed Aerobic Oxidative Synthesis of Quinazolinones from 2-Aminobenzamide and Methanol
Chatwichien, Jaruwan,Choommongkol, Vachira,Kerdphon, Sutthichat,Meepowpan, Puttinan,Rithchumpon, Puracheth,Sanghong, Patthadon,Singh, Thishana
, p. 2730 - 2734 (2020)
The focus of this study was the development of a new synthetic method for quinazolinones based on the principles of Green Chemistry. Quinazolinones were synthesized from 2-aminobenzamide using methanol as both the C1 source and a green solvent in the presence of base Cs2CO3. Additionally, a commercially available, economical copper complex was used as a catalyst in the reaction. The desired products were achieved in moderate to high yield with up to 99 % isolated yield.
Quinazolin-4(3H)-one-Based Hydroxamic Acids: Design, Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity
Hieu, Doan Thanh,Anh, Duong Tien,Hai, Pham-The,Thuan, Nguyen Thi,Huong, Le-Thi-Thu,Park, Eun Jae,Young Ji,Soon Kang, Jong,Phuong Dung, Phan Thi,Han, Sang-Bae,Nam, Nguyen-Hai
, (2019)
The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin-4(3H)-ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N-hydroxy-7-(7-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5b) and N-hydroxy-7-(6-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5c) (IC50 values, 0.10–0.16 μm) were found to be approximately 30-fold more cytotoxic than SAHA (IC50 values of 3.29–3.67 μm). N-Hydroxy-7-(4-oxoquinazolin-3(4H)-yl)heptanamide (5a; IC50 values of 0.21–0.38 μm) was approximately 10- to 15-fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC50 values in sub-micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c, strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.
Microwave-assisted Niementowski reaction. Back to the roots
Alexandre, Fran?ois-René,Berecibar, Amaya,Besson, Thierry
, p. 3911 - 3913 (2002)
In a search to speed up an aspect of the drug discovery processes, the Niementowski synthesis of the 3H-quinazolin-4-one core was reinvestigated using microwave irradiation. The experimental methodology and microwave conditions described here are well established, allowing significant rate enhancements and good yields compared to conventional reaction conditions.
Design, synthesis, and evaluation of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides as antitumor agents
Dung, Do T. M.,Park, Eun J.,Anh, Duong T.,Hai, Pham-The,Huy, Le D.,Jun, Hye W.,Kwon, Joo-Hee,Young Ji,Kang, Jong S.,Tung, Truong T.,Dung, Phan T. P.,Han, Sang-Bae,Nam, Nguyen-Hai
, (2021/10/25)
In our continuing search for novel small-molecule anticancer agents, we designed and synthesized a series of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides (5), focusing on the modification of substitution in the quinazolin-4(3H)-one moiety. The biological evaluation showed that all 13 designed and synthesized compounds displayed significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5l displayed cytotoxicity up to 213-fold more potent than 5-fluorouracil and 87-fold more potent than PAC-1, the first procaspase-activating compound. Structure–activity relationship analysis revealed that substitution of either electron-withdrawing or electron-releasing groups at positions 6 or 7 on the quinazolin-4(3H)-4-one moiety increased the cytotoxicity of the compounds, but substitution at position 6 seemed to be more favorable. In the caspase activation assay, compound 5l was found to activate the caspase activity by 291% in comparison to PAC-1, which was used as a control. Further docking simulation also revealed that this compound may be a potent allosteric inhibitor of procaspase-3 through chelation of the inhibitory zinc ion. Physicochemical and ADMET calculations for 5l provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent.
Visible-Light Photosynthesis of CHF2/CClF2/CBrF2-Substituted Ring-fused Quinazolinones in Dimethyl Carbonate
Gui, Qing-Wen,He, Wei-Min,Huang, Wen-Jie,Lu, Zi-Qin,Ouyang, Wen-Tao,Teng, Fan,Xun, Changping,Yang, Hao,Zhu, Meng-Xue
, (2021/12/01)
With eco-friendly and sustainable CO2-derived dimethyl carbonate as the sole solvent, the visible-light-induced cascade radical reactions have been established as a green and efficient tool for constructing various CHF2/CClF2/CBrF2-substituted ring-fused quinazolinones.
Quinazoline compound and application thereof
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Paragraph 0105-0107, (2021/05/12)
The invention relates to a quinazoline-containing compound as shown in a general formula (I), and a pharmaceutically acceptable salt, a solvate and a prodrug thereof, wherein substituent groups R1, R2, R3, R4, R5, R6, p, m and n are defined in the specification. The invention also relates to application of the compound shown in the general formula (I) in preparation of antitumor drugs, and also relates to application of the compound, the pharmaceutically acceptable salt, the solvate and the prodrug thereof in preparation and/or prevention and alleviation of cancers caused by tumor cells of human tissues or organs, wherein the cancers are preferably colon cancer, liver cancer, lymphoma, lung cancer, esophageal cancer, breast cancer, central nervous system tumor, melanoma, skin cancer, ovarian cancer, cervical cancer, kidney cancer, leukemia, prostate cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharyngeal cancer or gastric cancer and the like.
