- Reaction of 3-aminoquinoline-2,4-diones with nitrourea. Synthetic route to novel 3-ureidoquinoline-2,4-diones and imidazo[4,5-c]quinoline-2,4-diones
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1-Unsubstituted 3-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with 1-substituted and 1,1-disubstituted ureas in boiling acetic acid to give 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones. In contrast, the reaction of these amines with nitrourea in dioxane affords novel 3-alkyl/aryl-3-ureido-1H, 3H-quinoline-2,4-diones or 9b-hydroxy-3a-alkyl/aryl-3,3a,5,9b-tetrahydro-1H- imidazo[4,5-c]quinoline-2,4-diones, which can smoothly be dehydrated to 3a-alkyl/aryl-3,3a-dihydro-5H-imidazo[4,5-c]quinoline-2,4-diones. All three types of products can be converted to 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5- diones by refluxing in acetic acid. Graphical Abstract
- Klásek, Antonín,Ly?ka, Antonín,Hol?apek, Michal,Hoza, Ignác
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Read Online
- Synthesis of Benzofuranes by Cyclodehydrogenation of Phenylmalonyl Heterocyclic Compounds
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Phenylmalonyl heterocyclic compounds such as the quinolones 1a-c or 3, benzoquinolizinones 6a, b and the phenalenones 8a, b can be converted to benzofuranes (2a-c, 7a, b and 9a, b) by cyclodehydrogenation with Pd/C in boiling diphenyl ether. 2-Phenylchinc
- Stadlbauer, Wolfgang,Schmut, Otto,Kappe, Thomas
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Read Online
- Reaction of Tertiary 2-Chloroketones with Cyanide Ions: Application to 3-Chloroquinolinediones
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3-Chloroquinoline-2,4-diones react with cyanide ions in dimethyl formamide to give 3-cyanoquinoline-2,4-diones in small yields due to the strong hindrance of the substituent at the C-3 atom. Good yields can be achieved if the substituent at this position
- Bedná?, Luká?,Kafka, Stanislav,Klásek, Antonín,Ly?ka, Antonín,Rouchal, Michal,Rudolf, Ond?ej
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p. 645 - 652
(2021/07/22)
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- One-step Synthesis of 3-Unsubstituted 4-Hydroxy-2(1H)-Quinoline
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3-Unsubstituted 4-hydroxy-2(1H)-quinolone (DHQ) derivatives were synthesized from aniline derivatives and diethyl malonate at low temperature using AlCl3 as catalyst and Eaton reagent as acidic environment. A reaction mechanism was proposed and elucidated. Different synthetic intermediates are specially prepared or purified and used to understand the reaction and validation mechanism.
- Menglin, Ma,Qingrong, Sun,Weiqing, Yang,Xingyi, Wang,Yinan, Xu
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p. 435 - 441
(2021/11/22)
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- Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones
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In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 μM and against Mycobacterium bovis AN5A below 15 μM but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 μM and a CC50 against MRC-5 of 67.4 μM.
- de Macedo, Maíra Bidart,Kimmel, Roman,Urankar, Damijana,Gazvoda, Martin,Peixoto, Antonio,Cools, Freya,Torfs, Eveline,Verschaeve, Luc,Lima, Emerson Silva,Ly?ka, Antonín,Mili?evi?, David,Klásek, Antonín,Cos, Paul,Kafka, Stanislav,Ko?mrlj, Janez,Cappoen, Davie
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p. 491 - 500
(2017/07/10)
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- Structure activity relationships of 4-hydroxy-2-pyridones: A novel class of antituberculosis agents
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Pyridone 1 was identified from a high-throughput cell-based phenotypic screen against Mycobacterium tuberculosis (Mtb) including multi-drug resistant tuberculosis (MDR-TB) as a novel anti-TB agent and subsequently optimized series using cell-based Mtb ass
- Ng, Pearly Shuyi,Manjunatha, Ujjini H.,Rao, Srinivasa P.S.,Camacho, Luis R.,Ma, Ngai Ling,Herve, Maxime,Noble, Christian G.,Goh, Anne,Peukert, Stefan,Diagana, Thierry T.,Smith, Paul W.,Kondreddi, Ravinder Reddy
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p. 144 - 156
(2015/11/16)
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- Incorporation of carbon dioxide into molecules of acetylene hydrocarbons on heterogeneous Ag-containing catalysts
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The reaction between 2-(2-phenylethynyl)aniline and carbon dioxide on heterogeneous Ag-containing catalysts can lead either to benzoxazine-2-one or to 4-hydroxyquinoline-2(1Н)-one, depending on the reaction conditions (nature of the base, CO2 p
- Finashina,Tkachenko,Startseva, A. Yu.,Krasovsky,Kustov,Beletskaya
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p. 2796 - 2801
(2016/09/28)
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- Cu(i)-catalyzed chemical fixation of CO2 with 2-alkynylaniline into 4-hydroxyquinolin-2(1H)-one
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A copper(i) catalyzed reaction of 2-alkynylaniline with CO2 using DBU as base to produce 4-hydroxyquinolin-2(1H)-one derivatives in moderate to good yield is presented. In this reaction, a unique bond cleavage pattern for CO2 was observed that one of the C-O double bonds of CO 2 was totally broken and rearranged into two moieties in the absence of the reductive reagent. This efficient reaction system showed the wide generality of substrates including nitro, bromo, cyano and methoxylcarbonyl groups. A possible mechanism containing isocyanate intermediate is proposed. This journal is the Partner Organisations 2014.
- Guo, Chun-Xiao,Zhang, Wen-Zhen,Liu, Si,Lu, Xiao-Bing
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p. 1570 - 1577
(2014/06/09)
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- Oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones into N-(α-ketoacyl)anthranilic acids Dedicated to Professor Slovenko Polanc on his 65th birthday
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N-(α-Ketoacyl)anthranilic acids were prepared by oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones by using paraperiodic acid (H5IO6) or sodium periodate (NaIO4). The optimisation of the reaction conditions is
- Kafka, Stanislav,Proisl, Karel,Ka?párková, Věra,Urankar, Damijana,Kimmel, Roman,Ko?mrlj, Janez
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p. 10826 - 10835
(2014/01/06)
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- Efficient preparation of 4-hydroxyquinolin-2(1 H)-one derivatives with silver-catalyzed carbon dioxide incorporation and intramolecular rearrangement
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Although 4-hydroxyquinolin-2(1H)-one derivatives have attracted much attention due to their biological benefits, conventional reactions under harsh heat conditions must be employed to provide these key compounds. In the presence of a catalytic amount of s
- Ishida, Tomonobu,Kikuchi, Satoshi,Yamada, Tohru
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p. 3710 - 3713
(2013/08/23)
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- Reaction of some 2-quinolone derivatives with phosphoryl chloride: Synthesis of novel phosphoric acid esters of 4-hydroxy-2-quinolone
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3-Chloroquinoline-2,4-diones do not react with phosphoryl chloride, however, 2,4-dichloroquinolines and/or 4-chloroquinolin-2-ones are formed in the presence of N,N-dimethylaniline. Along with these compounds, small quantities of novel dihydrogen phosphates of 4-hydroxyquinolin-2-ones were isolated. We outline a simple procedure that allows for the preparation of these compounds in moderate to good yields. All compounds were characterized by 1H and 13C NMR, IR, EI-MS, and ESI-MS spectroscopy, and in select cases by 31P NMR spectroscopy.
- Rudolf, Ondrej,Mrkvicka, Vladimir,Lycka, Antonin,Rouchal, Michal,Klasek, Antonin
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p. E100-E110
(2013/06/04)
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- Catalyst-controlled divergent C-H functionalization of unsymmetrical 2-aryl cyclic 1,3-dicarbonyl compounds with alkynes and alkenes
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Achieving site-selective, switchable C-H functionalizations of substrates that contain several different types of reactive C-H bonds is an attractive objective to enable the generation of different products from the same starting materials. Herein, we dem
- Dooley, Johnathon D.,Reddy Chidipudi, Suresh,Lam, Hon Wai
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supporting information
p. 10829 - 10836
(2013/08/23)
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- Copper(I) iodide catalyzed synthesis of quinolinones via cascade reactions of 2-halobenzocarbonyls with 2-arylacetamides
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An efficient copper-catalyzed method for the synthesis of quinolinones, pyridinones, and heteroannulated pyridinones via cascade reactions of substituted 2-iodo-, 2-bromo-, and 2-chlorobenzocarbonyls with 2-arylacetamides is reported. The protocol works well for the reaction of most of the 2-iodo-, 2-bromo- and 2-chlorobenzocarbonyls with 2-arylacetamides. Georg Thieme Verlag Stuttgart · New York.
- Fu, Liangbing,Huang, Xiaoli,Wang, Deping,Zhao, Pinghua,Ding, Ke
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experimental part
p. 1547 - 1554
(2011/06/25)
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- Copper(I)-catalyzed [3+2] cycloaddition of 3-azidoquinoline-2,4(1H,3H)- diones with terminal alkynes
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3-Azidoquinoline-2,4(1H,3H)-diones 1,which are readily available from 4-hydroxyquinolin-2(1H)-ones 4 via 3-chloroquinoline-2,4(1H,3H)-diones 5, afford, in copper(I)-catalyzed [3+2] cycloaddition reaction with terminal acetylenes, 1,4-disubstituted 1,2,3-t
- Kafka, Stanislav,Hauke, Sylvia,Salcinovic, Arjana,Soidinsalo, Otto,Urankar, Damijana,Kosmrlj, Janez
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scheme or table
p. 4070 - 4081
(2011/07/30)
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- Selective formation of glycosidic linkages of N-unsubstituted 4-hydroxyquinolin-2-(1H)-ones
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A comparative study for selective glucosylation of N-unsubstituted 4-hydroxyquinolin-2(1H)-ones into 4-(tetra-O-acetyl-β-d-glucopyranosyloxy)quinolin-2(1H)-ones is reported. Four glycosyl donors including tetra-O-acetyl-α-d-glucopyranosyl bromide, β-d-glu
- Kimmel, Roman,Kafka, Stanislav,Ko?mrlj, Janez
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scheme or table
p. 768 - 779
(2010/06/14)
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- INHIBITORS OF FATTY ACID SYNTHASE (FAS)
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The instant invention provides for compounds which comprise substituted 3-aryl-4-hydroxyquinolin-2(1H)-ones that inhibit FAS activity. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting FAS activity
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Page/Page column 28-29
(2008/06/13)
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- 3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors
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A series of 3-aryl-4-hydroxyquinolin-2(1H)-ones with fatty acid synthase inhibitory activity was prepared. Starting from a derivative with an IC50 = 1.4 μM, SAR studies led to compounds with more than 70-fold increase in potency (IC50/sub
- Rivkin, Alexey,Kim, Yoona R.,Goulet, Mark T.,Bays, Nathan,Hill, Armetta D.,Kariv, Ilona,Krauss, Stefan,Ginanni, Nicole,Strack, Peter R.,Kohl, Nancy E.,Chung, Christine C.,Varnerin, Jeffrey P.,Goudreau, Paul N.,Chang, Amy,Tota, Michael R.,Munoz, Benito
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p. 4620 - 4623
(2007/10/03)
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- Solvent-free microwave synthesis of 4-hydroxy-3-phenylquinolin-2(1H)-ones and variants using activated arylmalonates
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The disclosure herein describes the rapid synthesis of 4-hydroxy-3-phenylquinolin-2(1H)-ones and variants via a solvent-free microwave cyclocondensation reaction using di-(2,4,6-trichlorophenyl)-2-phenylmalonate, which improves the general scope of this reaction.
- Rivkin, Alexey,Adams, Bruce
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p. 2395 - 2398
(2007/10/03)
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- A new synthesis of naphthyridinones and quinolinones: Palladium-catalyzed amidation of o-carbonyl-substituted aryl halides
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(Equation Presented) An alternative to the Friedlander condensation for the synthesis of naphthyridinones and quinolinones has been discovered. Palladium-catalyzed amidation of halo aromatics substituted in the ortho position by a carbonyl functional group or its equivalent with primary or secondary amides leads to the formation of substituted naphthyridinones and quinolinones.
- Manley, Peter J.,Bilodeau, Mark T.
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p. 2433 - 2435
(2007/10/03)
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- An efficient route to 3-aryl-substituted quinolin-2-one and 1,8-naphthyridin-2-one derivatives of pharmaceutical interest
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Reaction of arylacetic ester enolates with 2-alkoxy-4H-3,1-benzoxazin-4-ones offers a short and versatile synthetic route to 3-aryl-4-hydroxyquinolin-2(1H)-ones, through the cyclization of the β-ketoesters produced. Similar reactions of 4H-pyrido[2,3-d][1
- Mitsos, Christos A.,Zografos, Alexandros L.,Igglessi-Markopoulou, Olga
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p. 4567 - 4569
(2007/10/03)
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- Rapid microwave-enhanced synthesis of 4-hydroxyquinolinones under solvent-free conditions
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3-Aryl-4-hydroxyquinolin-2(1H)-ones are potent and selective glycine-site NMDA receptor antagonists of pharmaceutical interest. A novel microwave-enhanced synthesis of such quinolinones under solvent-free conditions has been developed. The quinolinones ar
- Lange, Jos H.M.,Verveer, Peter C.,Osnabrug, Stefan J.M.,Visser, Geb M.
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p. 1367 - 1369
(2007/10/03)
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- Solution-phase combinatorial synthesis of 4-hydroxyquinolin-2(1H)-ones
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Ion-exchange resins catalyse an intramolecular Claisen-type condensation leading to the title compounds, and also serve to purify the products.
- Kulkarni, Bheemashankar A.,Ganesan
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p. 785 - 786
(2007/10/03)
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- Synthesis of 4-Hydroxy-2(1H)-pyridones from Azomethines and Substituted Dialkylmalonates
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The reaction of azomethines 4 with substituted dialkyl malonates 5 leads to the formation of 3-substituted 4-hydroxy-2(1H)-pyridones 6 in moderate yields. The azomethines 4 are prepared via arylaminopropionitriles 3 or in the conventional way by acid catalyzed condensation of ketones 1 with anilines 2. Chlorination of pyridones 6 with sulfuryl chloride leads to compounds 8-10.
- Kafka,Kappe
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p. 1019 - 1031
(2007/10/03)
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- Effect of plasma protein binding-on in vivo activity and brain penetration of glycine/NMDA receptor antagonists
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A major issue in designing drugs as antagonists at the glycine site of the NMDA receptor has been to achieve good in vivo activity. A series of 4- hydroxyquinolone glycine antagonists was found to be active in the DBA/2 mouse anticonvulsant assay, but improvements in in vitro affinity were not mirrored by corresponding increases in anticonvulsant activity. Here we show that binding of the compounds to plasma protein limits their brain penetration. Relative binding to the major plasma protein, albumin, was measured in two different ways: by a radioligand binding experiment or using an HPLC assay, for a wide structural range of glycine/NMDA site ligands. These measures of plasma protein binding correlate well (r = 0.84), and the HPLC assay has been used extensively to quantify plasma protein binding. For the 4-hydroxyquinolone series, binding to plasma protein correlates (r = 0.92) with log P (octanol/pH 7.4 buffer) over a range of log P values from 0 to 5. The anticonvulsant activity increases with in vitro affinity, but the slope of a plot of pED50 versus pIC50 is low (0.40); taking plasma protein binding into account in this plot increases the slope to 0.60. This shows that binding to albumin in plasma reduces the amount of compound free to diffuse across the blood-brain barrier. Further evidence comes from three other experiments: (a) Direct measurements of brain/blood ratios for three compounds (2, 16, 26) show the ratio decreases with increasing log P. (b) Warfarin, which compotes for albumin binding sites dose-dependently, decreased the ED50 of 26 for protection against seizures induced by NMDLA. (c) Direct measurements of brain penetration using an in situ brain perfusion model in rat to measure the amount of drug crossing the blood-brain barrier showed that compounds 2, 26, and 32 penetrate the brain well in the absence of plasma protein, but this is greatly reduced when the drug is delivered in plasma. In the 4-hydroxyquinolones glycine site binding affinity increases with lipophilicity of the 3-substituent up to a maximum at a log P around 3, then does not improve further. When combined with increasing protein binding, this gives a parabolic relationship between predicted in vivo activity and log P, with a maximum log P value of 2.39. Finally, the plasma protein binding studies have been extended to other series of glycine site antagonists, and it is shown that for a given log P these have similar protein binding to the 4-hydroxyquinolones, except for compounds that are not acidic. The results have implications for the design of novel glycine site antagonists, and it is suggested that it is necessary to either keep log P low or pK(a) high to obtain good central nervous system activity.
- Rowley, Michael,Kulagowski, Janusz J.,Watt, Alan P.,Rathbone, Denise,Stevenson, Graeme I.,Carling, Robert W.,Baker, Raymond,Marshall, George R.,Kemp, John A.,Foster, Alan C.,Grimwood, Sarah,Hargreaves, Richard,Hurley, Catherine,Saywell, Kay L.,Tricklebank, Mark D.,Leeson, Paul D.
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p. 4053 - 4068
(2007/10/03)
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- Synthesis of Coumarins and Quinolones by Intramolecular Aldol Condensation Reactions of Titanium Enediolates
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Low-valent titanium prepared by the reduction of TiCl3 with zinc dust oxidatively adds to α-ketoamides or α-ketoesters with the formation of the corresponding titanium enediolates.These 1,2-difunctional nucleophiles, which have hardly been used in organic
- Fuerstner, Alois,Jumbam, Denis N.,Shi, Nongyuan
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p. 326 - 332
(2007/10/02)
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- 4-HYDROXY-2-QUINOLONES. 2. SIMPLE SYNTHESIS OF ARBORICINE
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Acylation of methyl N-methylanthranilate with phenylacetyl chloride with subsequent intramolecular cyclization of the resulting anilide was used to synthesize 1-methyl-3-phenyl-4-hydroxy-2-quinolone (abroricine).
- Bezuglyi, P. A.,Ukrainets, I. V.,Treskach, V. I.,Turoy, A. V.
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p. 438 - 439
(2007/10/02)
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