- Synthesis of 3-alkylquinoxalin-2(1H)-ones via Grignard reaction
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A two-step procedure has been developed for the synthesis of 3-alkylquinoxalin-2(1H)-ones from o-phenylenediamine and ethyl 2-oxoalkanoates prepared by the Grignard reaction of diethyl oxalate with alkyl bromides. Analogous reaction with α,ω-dibromoalkanes instead of alkyl bromides leads to the formation of 3,3'-(alkane-α,ω-diyl)di[quinoxalin-2(1H) -ones].
- Kalinin,Mamedov
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- Design, synthesis, and evaluation of alkyl-quinoxalin-2(1h)-one derivatives as anti-quorum sensing molecules, inhibiting biofilm formation in aeromonas caviae Sch3
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With the increasing antibiotic resistance of bacterial strains, alternative methods for infection control are in high demand. Quorum sensing (QS) is the bacterial communication system based on small molecules. QS is enables bacterial biofilm formation and pathogenic development. The interruption of QS has become a target for drug discovery, but remains in the early experimental phase. In this study, we synthesized a set of six compounds based on a scaffold (alkyl-quinoxalin-2(1H)-one), new in the anti-QS of Gram-negative bacteria Aeromonas caviae Sch3. By quantifying biofilm formation, we were able to monitor the effect of these compounds from concentrations of 1 to 100 μM. Significant reduction in biofilm formation was achieved by 3-hexylylquinoxalin-2(1H)-one (11), 3-hexylylquinoxalin-2(1H)-one-6-carboxylic acid (12), and 3-heptylylquinoxalin-2(1H)-one-6-carboxylic acid (14), ranging from 11% to 59% inhibition of the biofilm. This pilot study contributes to the development of anti-QS compounds to overcome the clinical challenge of resistant bacteria strains.
- Bl?cher, René,Ramírez, Ariel Rodarte,Castro-Escarpulli, Graciela,Curiel-Quesada, Everardo,Reyes-Arellano, Alicia
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- Lithiation and Side-Chain Substitution of 3-Alkyl-1H-quinoxalin-2-ones
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3-Methyl-1H-quinoxalin-2-one has been doubly lithiated with n-butylithium at -78° C in THF. The dilithio reagent thus obtained reacts with various electrophiles (iodomethane, iodoethane, D2O, benzaldehyde, benzophenone, cyclohexanone) to give modified 3-substituted 1H-quinoxalin-2- ones in good yields. In the reaction of the dilithio reagent with phenyl isothiocyanate the product was a tautomer of the simple substitution product. Reaction of the dilithio reagent with iodine gives an oxidatively dimerised product instead of the 3-iodomethyl derivative. Lithiations of 3-ethyl-and 3-propyl-1H-quinoxalin-2-ones, followed by reactions with representative electrophiles (benzaldehyde, benzophenone, cyclohexanone), behaved in a similar manner to give the corresponding modified 3-substituted derivatives in good yields.
- Smith, Keith,El-Hiti, Gamal A.,Mahgoub, Safaa A.
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- Synthesis and functionalization of 3-ethylquinoxalin-2(1H)-one
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A new and effective procedure was developed for the synthesis of 3-ethylquinoxalin-2(1H)-one from o-phenylenediamine and ethyl 2-oxobutanoate. The latter was prepared by the Grignard reaction of diethyl oxalate with ethylmagnesium bromide or iodide. The ethyl group in 3-ethylquinoxalin-2(1H)-one can readily be converted into various functional groups: α-bromoethyl, α-thiocyanato, α-azidoethyl, α-phenylaminoethyl, acetyl, and bromoacetyl. The reaction of 3-(bromoacetyl)quinoxalin-2(1H)-one with thiourea and hydrazine-1,2-dicarbothioamide gives the corresponding 3-(2-amino-4- thiazolyl) derivatives.
- Mamedov,Kalinin,Gubaidullin,Isaikina,Litvinov
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- Synthesis of potential chemotherapic quinoxalinone derivatives by biocatalysis or microwave-assisted Hinsberg reaction
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In recent years, great efforts have been dedicated to the design of compounds acting as selective inhibitors of the HIV-1 reverse transcriptase (RT). Due to the promissory results previously attained with some quinoxaline derivatives, we aimed to improve the specific standard Hinsberg synthetic pathway by means of biocatalysis or microwave (MW) irradiation. Both techniques rendered the products in very good yields. However, employing the microwave-assisted organic synthesis (MAOS), in the absence of solvent, the same reactions may be completed in minutes. Some of these quinoxalinone derivatives exhibited good inhibitor activity against some human tumoral cells and the lymphoma related to HIV-1.
- Gris, Javier,Glisoni, Romina,Fabian, Lucas,Fernández, Beatriz,Moglioni, Albertina G.
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- Preparation method of quinoxalinone derivatives
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The invention belongs to the field of organic synthetic chemistry. The invention relates to a preparation method of quinoxalinone derivatives. Specifically, a covalent organic framework material 2D-COF-1 is used as a photocatalyst; and the quinoxaline-2 (
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Paragraph 0117-0120
(2019/12/02)
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- Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress
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We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40–Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4.
- Loughran, H. Marie,Han, Ziying,Wrobel, Jay E.,Decker, Sarah E.,Ruthel, Gordon,Freedman, Bruce D.,Harty, Ronald N.,Reitz, Allen B.
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supporting information
p. 3429 - 3435
(2016/07/21)
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- Structure-Activity Relationships of Quinoxaline-Based 5-HT3A and 5-HT3AB Receptor-Selective Ligands
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Until recently, discriminating between homomeric 5-HT3A and heteromeric 5-HT3AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2-chloro-3-(4-methylpiperazin-1-yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83-fold difference in [3H]granisetron binding affinity between 5-HT3A and 5-HT3AB receptors. Fragment hit exploration, initiated from VUF10166 and 3-(4-methylpiperazin-1-yl)quinoxalin-2-ol, resulted in a series of compounds with higher affinity at either 5-HT3A or 5-HT3AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2-amino-3-(4-methylpiperazin-1-yl)quinoxaline, which showed 11-fold selectivity for the 5-HT3A receptor, and 2-(4-methylpiperazin-1-yl)quinoxaline, which showed an 8.3-fold selectivity for the 5-HT3AB receptor. These compounds represent novel molecular tools for studying 5-HT3 receptor subtypes and could help elucidate their physiological roles.
- Thompson, Andrew J.,Verheij, Mark H. P.,VanMuijlwijk-Koezen, Jacqueline E.,Lummis, Sarah C. R.,Leurs, Rob,DeEsch, Iwan J. P.
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p. 946 - 955
(2013/07/27)
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- QUINOXALINONE-3- ONE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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The invention relates to quinoxalinone derivatives of general Formula (I) and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.General Formula (I) wherein X and R1-R9 are as defined in the description
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