- Structure, preparation method and application of quinoxalinone derivative
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The invention provides a structure and preparation of a quinoxalinone derivative (a compound as shown in formula I) and application of the pharmaceutically acceptable salt of the quinoxalinone derivative in the preparation of drugs for preventing and/or treating diabetic complication. The quinoxalinone derivative serving as a aldose reductase inhibitor and antioxidant can prevent and/or treat thediabetic complication by inhibiting the activity of aldose reductase and effectively scavenging free radicals and lipid peroxide and inhibiting active oxygen at the same time.
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- Structure, preparation method and application of a series of quinoxalinone derivatives
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The invention provides the structure and synthesis method of a compound shown in the formula I, and application of pharmaceutically acceptable salts of the compound or a mixture of the salts in preparation of drugs for preventing and/or treating diabetic complications. The compound acts as aldose reductase inhibitors and antioxidants and can effectively scavenge free radicals and inhibit the production of lipid peroxides by inhibiting the activity of aldose reductase, and thus the effect of preventing and/or treating the diabetic complications is achieved. The invention further provides a pharmaceutical composition containing the compound and having preventive and/or therapeutic effects on diabetic complications. The formula can be seen in the description.
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- Exploration of quinoxaline derivatives as antimicrobial and anticancer agents
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Novel 2 and 3-substituted quinoxaline derivatives were synthesized through various synthetic pathways, among which cyanoacetamide and cyanoacetohydrazide quinoxaline derivatives 4a-c and 11a-c, respectively, were synthesized. Furthermore, methoxy quinoxaline derivatives 3c and quinoxaline derivatives bearing substituted pyridines 6a,b, 12a,b, and 13a,b were designed to be synthesized. However, we have synthesized acrylohydrazide 5a,b and 7/acrylamide derivatives, Schiff base analogues 14a-f, pyrazole derivatives 15a-e, amide derivatives 16a-f, guanidine derivatives 16 g,h as well as, quinoxalin-2-methylallyl propionate derivative 14g. All the synthesized compounds were confirmed via spectral data and elemental analyses. Moreover, the newly synthesized compounds were evaluated for their antimicrobial activity (Gm +ve, Gm ?ve in comparison to Gentamycin a standard) and fungi (in comparison to Ketoconazole as a standard). Thus, compound 16b showed promising antimicrobial activity against B. subtilis, P. vulgaris, and S. mutants with values ranging from 20 to 27-mm zone of inhibition. While compounds 5a, 14e,f, and 16a,c,d,g,h showed potent antimicrobial activity. Moreover, the National Cancer Institute (NCI) selected 20 compounds that were submitted for anticancer screening against 60 types of cancer cell lines. The most active compounds are 5b and 12a where compound 5b containing 2,4-dichlorophenyl moiety at cyanoacetamide linkage of hydrazine quinoxaline backbone exerted significant growth inhibition activity against Leukemia MOLT-4, Renal cancer UO-31, and Breast cancer MCF-7. In addition, compound 12a having 4,6-diaminopyridinone side chain at position-3 of quinoxaline nucleus exhibited remarkable anticancer activity against renal cancer UO-31.
- Bayoumi, Ashraf H.,Ghiaty, Adel H.,Abd El-Gilil, Shimaa M.,Husseiny, Ebtehal M.,Ebrahim, Maha A.
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p. 3215 - 3235
(2019/11/16)
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- DNA topoisomerase II inhibition has the activity of modulating kui analogue and its preparation method and application
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The invention discloses a quinoxalinone analog with DNA (deoxyribonucleic acid) topoismerase II inhibiting activity, an optical isomer, diastereoisomer or racemic mixture, or pharmaceutically acceptable salt, solvate, prodrug, intermediate or metabolite thereof. The structural general formula is disclosed as Formula (I), wherein R1, R2, R3, R4, R5 and Ar are defined in the specification. The invention also discloses a preparation method of the compounds and application of the compounds as drugs and in treating tumors. The compounds have the advantages of definite curative effect and small toxic and side effects, enriches the varieties of inhibitors of drugs for treating diseases caused by topoismerase II expression abnormity in the prior art, and is hopeful to become clinical drugs with higher therapeutic index.
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Paragraph 0144; 0149; 0150
(2018/08/03)
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- Design, synthesis and structure-activity relationship of novel quinoxaline derivatives as cancer chemopreventive agent by inhibition of tyrosine kinase receptor
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The cancer chemopreventive activity of quinoxaline derivatives 1-20 has been evaluated by studying the inhibitory effect on Epstein-Barr virus early antigen (EBV-EA) activation. The quinoxaline derivatives 1-20 showed inhibitory effect on EBV-EA activation without cytotoxicity on Raji cells. All compounds exhibited dose dependent inhibitory activities, most of them showed significant activity at 1000 mol ratio/12-O-tetradecanoylphorbol-13-acetate (TPA). Compounds 7 and 9 exhibited stronger inhibitory effects on the EBV-EA activation than that of the representative control, oleanolic acid, at the highest measured concentration. In addition, compounds 7-10 showed potent and selective inhibition of human tyrosine kinase (TRK) in liver cancer HepG2 and breast cancer MCF-7 cell lines similar to the positive control, doxorubicin.
- Galal, Shadia A.,Abdelsamie, Ahmed S.,Soliman, Salwa M.,Mortier, Jeremie,Wolber, Gerhard,Ali, Mamdouh M.,Tokuda, Harukuni,Suzuki, Nobutaka,Lida, Akira,Ramadan, Raghda A.,El Diwani, Hoda I.
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p. 115 - 124
(2013/10/01)
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- METHOD FOR PREPARING SUBSTITUTED N-(3-AMINO-QUINOXALIN-2-YL)-SULFONAMIDES AND THEIR INTERMEDIATES N-(3-CHLORO-QUINOXALIN-2-YL)SULFONAMIDES
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The present invention provides a new synthesis for preparing N-(3-amino-quinoxalin-2-yl)-sulfonamides of general formulae (I) or (I') and intermediates sulfonamides of formula (II) or (II'):
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Page/Page column 24-25
(2012/05/05)
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- An Efficient Synthesis of Quinoxalinone Derivatives as Potent Inhibitors of Aldose Reductase
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A novel and facile synthesis of quinoxalinone derivatives was developed in which a wide range of 3-chloroquinoxalin-2(1H)-ones as key intermediates can be generated chemo- and regioselectively in good yields from corresponding quinoxaline-2,3(1H,4H)-diones. This new protocol is arguably superior, as it allows the design and preparation of a variety of bioactive quinoxaline-based compounds, which are particularly effective in the treatment of diabetes and its complications. Through this procedure, a new class of quinoxalinone-based aldose reductase inhibitors were synthesized successfully. Most of the inhibitors, with an N1-acetic acid head group and a substituted C3-phenoxy side chain, proved to be potent and selective. Their IC50 values ranged from 11.4 to 74.8nM. Among them, 2-(3-(4-bromophenoxy)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid and 2-(6-bromo-3-(4-bromophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid were the most active. Structure-activity relationship and molecular docking studies highlighted the importance of the ether spacer in the C3-phenoxy side chains, and provided clear guidance on the contribution of substitutions both at the core structure and the side chain to activity.
- Yang, Yanchun,Zhang, Shuzhen,Wu, Bobin,Ma, Mingming,Chen, Xin,Qin, Xiangyu,He, Minlan,Hussain, Saghir,Jing, Chaojun,Ma, Bing,Zhu, Changjin
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p. 823 - 835
(2012/07/17)
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- Synthesis and antimicrobial activity of novel thiazolidinone and azetidinone derivatives
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Reaction of 2,3-diketoquinoxaline in presence of phosphorus pentachloride and hydrazine hydrate gives 2-hydrazino-3-hydroxyquinoxalin (4) which on treatment with various aldehydes in appropriate solvent gives 2-p-anisyl-3-(3-hydroxy quinoxalin-2 yl-amino)-4-thiazolidinones (6) and 1-N-(3-hydroxy quinoxalin-2'yl-amino)-4-aryl-3-chloro-2-azetidinones (7). The structure of compounds 6a-6l and 7a-7l has been confirmed by IR and 1H NMR data. All these compounds were tested for their antimicrobial and antifungal activity against different microorganisms.
- Kshirsagar,Nimje,Chaudhari,Bayas,Patel,Karjikar,Girme,Oswal
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experimental part
p. 4021 - 4023
(2012/01/12)
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- Part I: Synthesis, cancer chemopreventive activity and molecular docking study of novel quinoxaline derivatives
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The reaction of o-phenylene diamine and ethyl oxamate is reinvestigated and led to 3-aminoquinoxalin-2(1H)-one rather than benzimidazole-2-carboxamide as was previously reported. The structure of the obtained quinoxaline has been confirmed by X-ray. The anti-tumor activity of synthesized quinoxalines 1-21 has been evaluated by studying their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13- acetate (TPA). Among the studied compounds 1-21, compounds 12, 8, 13, 18, 17 and 19, respectively, demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity and their effects being stronger than that of a representative control, oleanolic acid. Furthermore, compound 12 exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The result of the present investigation indicated that compound 12 might be valuable as a potent cancer chemopreventive agent. Moreover, the molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors.
- Galal, Shadia A.,Abdelsamie, Ahmed S.,Tokuda, Harukuni,Suzuki, Nobutaka,Lida, Akira,Elhefnawi, Mahmoud M.,Ramadan, Raghda A.,Atta, Mona H.E.,El Diwani, Hoda I.
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experimental part
p. 327 - 340
(2011/02/25)
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- Synthesis of some 4-substituted hydrazinotetrazolo[1,5-a]quinoxalines
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Reaction of 2,3 diketoquinoxaline in presence of phosphorus pentachloride and sodium azide in methanol gives 4-hydroxy tetrazolo[1,5-a]quinoxaline 3 which on reaction with phosphorous oxychloride gives 4-chloro tetrazolo[1,5-a] quinoxaline 4. This on treatment with hydrazine hydrate in ethanol yields 4-hydrazino tetrazolo[1,5-a]quinoxaline 5, which on reaction with various aldehydes in DMF gives 4-substituted hydrazinotetrazolo [1,5-a]quinoxalines 6a-g. The structures of compounds 6a-g have been confirmed by IR and 1H NMR.
- Deshmukh,Mali,Jadhav,Suryawanshi
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p. 1211 - 1213
(2008/09/18)
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- Synthesis and evaluation of 3-anilino-quinoxalinones as glycogen phosphorylase inhibitors
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A series of 3-anilino-quinoxalinones has been identified as a new class of glycogen phosphorylase inhibitors. The lead compound 1 was identified through high throughput screening as well as through pharmacophore-based electronic screening. Modifications were made to the scaffold of 1 to produce novel analogues, some of which are 25 times more potent than the lead compound.
- Dudash Jr., Joseph,Zhang, Yongzheng,Moore, John B.,Look, Richard,Liang, Yin,Beavers, Mary Pat,Conway, Bruce R.,Rybczynski, Philip J.,Demarest, Keith T.
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p. 4790 - 4793
(2007/10/03)
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- Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors
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The present invention relates to compounds of Formula I or II, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 37
(2008/06/13)
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- 1,2,4-Triazolo[4,3-a]quinoxaline-1,4-diones as antiallergic agents
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A series of new 1,4-dihydro-1,2,4-triazolo[4,3-a]quinoxaline-1,4-diones has been reported. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated rat passive cutaneous anaphylaxis (PCA). Most of this new class of antiallergic agents showed good activity in the RMC and PCA tests. The most potent compound, 2-acetyl-7-chloro-5-n-propyl-1,2,4-triazolo[4,3-a]quinoxaline-1,4-dione, with an I50 value of 0.1 μM, is 30 times more potent than disodium cromoglycate (DSCG) in the RMC assay.
- Loev,Musser,Brown,Jones,Kahen,Huang,Khandwala,Sonnino-Goldman,Leibowitz
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p. 363 - 366
(2007/10/02)
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