- Iodine-Catalyzed Oxidative Cross-Dehydrogenative Coupling of Quinoxalinones and Indoles: Synthesis of 3-(Indol-2-yl)quinoxalin-2-one under Mild and Ambient Conditions
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A highly efficient iodine-catalyzed oxidative cross-dehydrogenative coupling reaction of quinoxalinones and indoles has been developed. Without the requirement of peroxide and acid, this reaction utilizes a catalytic amount of molecular iodine to facilitate the C-C bond formation under ambient air. This simple and easy-to-handle protocol represents an interesting synthetic alternative with a good scope and functional group compatibility.
- Noikham, Medena,Kittikool, Tanakorn,Yotphan, Sirilata
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- Micellar effects upon the reaction of hydroxide ion with 2-phenoxyquinoxaline
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Cationic micelles of alkyltrimethylammonium chloride and bromide (alkyl = n - C12H25, n - C14H29, and n - C16H33) catalyze and anionic micelles of sodium dodecyl sulfate inhibit the reaction of hydroxide ion with 2-phenoxyquinoxaline (1). Inert anions such as chloride, nitrate, mesylate, and n-butanosulfonate inhibit the reaction in CTABr by competing with OH- at the micellar surface. The overall micellar effects on rate in cationic micelles and dilute electrolyte can be treated quantitatively in terms of the pseudo-phase ion-exchange model. The determined second-order rate constants in the micellar pseudo-phase are smaller than the second-order constants in water.
- Cuenca,Bruno
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- Synthesis of 2-(4-nitrophenoxy)quinoxaline and its reactions with hydroxide ion in micellar systems
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The synthesis of 2-(4-nitrophenoxy)quinoxaline (3) is described. The reaction of (3) with hydroxide ion was studied in the presence and absence of micellar systems. Cationic micelles of cetyltrimethylammonium chloride and bromide (CTACl and CTABr) and tetradecyltrimethylammonium chloride and bromide (MTACl and MTABr) speed the reaction of (3) with hydroxide ion. The second-order rate constants at the micellar pseudophase are smaller than the second-order rate constant in water.
- Cuenca, Angela,Bruno, Cesidio,Taddei, Antonieta
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- Chemoselective synthesis of 3,6,7-trisubstituted 2-(2,3:5,6-di-O-isopropylidene-β-D-mannofuranosyloxy]- and 2-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyloxy)quinoxaline derivatives
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[Figure not available: see fulltext.] A series of quinoxaline O-nucleosides, 3,6,7-trisubstituted 2-(2,3:5,6-di-O-isopropylidene-β-D-mannofuranosyl-1-yl)quinoxalines and 2-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-β-D-glucopyranosyl)quinoxalines, was prepared by the reaction of 3,6,7-trisubstituted quinoxalin-2(1H)-ones with the corresponding protected α-chlorosugars in the presence of NaH. The reaction proceeded chemoselectively to give products of O-substitution with β-configuration at anomeric carbon, as proved by NMR data. The deprotection of the 1-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-β-D-glucopyranosyl)quinoxalines was achieved by stirring in ammonia-methanol mixture to afford free O-quinoxaline nucleoside analogs.
- Fathalla, Walid
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- Synthesis of (E)-Quinoxalinone Oximes through a Multicomponent Reaction under Mild Conditions
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Herein, a novel method for the gram-scale synthesis of (E)-quinoxalinone oximes through a multicomponent reaction under mild conditions is described. Such a transformation was performed under transition-metal-free conditions, affording (E)-oximes in a moderate-to-good yield through recrystallization. Our methodology demonstrates a successful combination of a Mannich-type reaction and radical coupling, providing a green and practical approach for the synthesis of potentially bioactive quinoxalinone-containing molecules.
- Xu, Jun,Yang, Huiyong,He, Lei,Huang, Lin,Shen, Jiabin,Li, Wanmei,Zhang, Pengfei
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- Electrochemically C-H/S-H Oxidative Cross-Coupling between Quinoxalin-2(1 H)-ones and Thiols for the Synthesis of 3-Thioquinoxalinones
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An electrochemical method for the C(sp2)-H thioetherification of quinoxalin-2(1H)-ones with primary, secondary, and tertiary thiols has been reported. Various quinoxalin-2(1H)-ones underwent this thioetherification smoothly under metal- A nd chemical oxidant-free conditions, affording 3-alkylthiol-substituted quinoxalin-2(1H)-ones in moderate to good yields.
- Zhou, Jiadi,Li, Zhonghui,Sun, Zexu,Ren, Quanlei,Zhang, Qiwei,Li, Hu,Li, Jianjun
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- Tosvinyl and besvinyl as protecting groups of imides, azinones, nucleosides, sultams, and lactams. Catalytic conjugate additions to tosylacetylene
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The use of the 2-(4-methylphenylsulfonyl)-ethenyl (tosvinyl, Tsv) group for the protection of the NH group of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examined. The Tsvprotected derivatives are obtained in excellent yields by conjugate addition to tosylacetylene (ethynyl p-tolyl sulfone). The stereochemistry of the double bond can be controlled at will: with only 1 mol % of Et3N or with catalytic amounts of NaH, the Z stereoisomers are generated almost exclusively, while the E isomers are obtained using a stoichiometric amount of DMAP. Analogous phenylsulfonylvinyl-protected groups (with the besvinyl or Bsv group instead of Tsv) are obtained stereospecifically by reaction with (Z)- or (E)-bis(phenylsulfonyl)ethene. For lactams and oxazolidinones, this last method is much better. The Tsv and Bsv groups are stable in the presence of non-nucleophilic bases and to acids. They can be removed highly effectively via a conjugate addition-elimination mechanism using pyrrolidine or sodium dodecanethiolate as nucleophiles.
- Petit, Elena,Bosch, Llus,Font, Joan,Mola, Laura,Costa, Anna M.,Vilarrasa, Jaume
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- Electrochemically dehydrogenative C-H/P-H cross-coupling: Effective synthesis of phosphonated quinoxalin-2(1: H)-ones and xanthenes
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An efficient electrochemical approach for the C(sp2)-H phosphonation of quinoxalin-2(1H)-ones and C(sp3)-H phosphonation of xanthenes has been developed. The chemistry was performed in an undivided cell under constant current conditions and features a wide range of substrates, up to 99% yield and it is free of transition-metal catalysts- A nd external oxidants, thereby providing a straightforward approach for dehydrogenative C-H/P-H cross-coupling. In addition, control experiments disclose that some of the reactions may involve a radical pathway.
- Li, Ke-Jing,Jiang, Yang-Ye,Xu, Kun,Zeng, Cheng-Chu,Sun, Bao-Guo
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- UNPRODUCTIVE SIGMA AND PI COMPLEXES IN THE REACTION OF 2-CHLOROQUINOXALINE WITH PIPERIDINE IN DIMETHYL SULPHOXIDE
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The rate of the reaction of 2-chloroquinoxaline with piperidine in dimethyl sulphoxide was measured over a wide range of amine concentrations and at several temperatures.It was found that the order with respect to the nucleophile is close to 1 between 300 and 320 K, but is definitely less at lower and higher temperatures.It is suggested that below 300 K an unreactive charge-transfer complex is formed between the reactants which dissociates at higher temperatures, whereas at temperatures higher than 320 K an unproductive ? complex is formed, the concentration of which increases with increase in temperature.
- Nasielski, J.,Rypens, C.
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- Surfactant effects on the reaction of 2-(4-cyano-phenoxy)-quinoxaline with hydroxide ion
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A reaction of 2-(4-cyanophenoxy)quinoxaline 1 with hydroxide ion is accelerated by supramolecular aggregates of cetyltrialkylammonium chlorides (alkyl = Me. n-Pr. and n-Bu). In diluted surfactant solutions, with relatively high substrate concentration (7.0 × 10-5 M). rate constants go through double rate maxima with increase in the surfactant concentration. The first rate maximum is ascribed to a reaction occurring in premicellar aggregates and the second to reaction in micelles. At low substrate concentration (7×10-6 M), second-order rate constants in the micellar pseudophase are dependent on the surfactant head-group size, which is related to charge dispersion in the transition state. Nonmicellizing tri-n- octylmethylammonium ions (TOAMs) increase the reaction of 1 with hydroxide ion. The observed rate enhancements may be due to the formation of small. Hydrophobic aggregates which bind the substrate and promote the nucleophilic substitution reaction.
- Cuenca, Angela
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- Rapidly formed quinalphos complexes with transition metal ions characterized by electrospray ionization mass spectrometry
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RATIONALE Electrospray ionization tandem mass spectrometry (ESI-MS/MS) offers the unique opportunity to characterize complexes of the organophosphorus pesticide (OP) quinalphos (PA-Q) with transition metal ions immediately formed after contact. This study complements research looking at longer term kinetics of quinalphos hydrolysis in the presence of transition metal ions and gives insights into the structural features of the initial complex formation in solution. (Hydrolysis reaction: PA-Q + H2O → PA-OH + HQ, where PA-OH is the diethyl phosphate product and HQ is hydroxyquinoxaline.) METHODS Low micromolar PA-Q solutions with an approximately 3-fold molar excess of transition metal ions were immediately analyzed after mixing. Fragmentation of the transition metal ion complexes with PA-Q was accomplished in two different ways: first, in-source fragmentation by elevating the declustering potential and second, low-energy collision-induced dissociation (CID). RESULTS For Ag +, the [PA-Q - Ag+] and respective Ag+- containing degradation product ions are readily observed. For Cu2+, we observed the [PA-Q + Cu2+ + NO3-] complex ion with weak intensity and strong signals from both the [2PA-Q + Cu +] and the [PA-Q + Cu+] ions, the latter two attributable to charge-state reduction in the gas phase from Cu(II) to Cu(I), indicating that PA-Q fulfills specific structural requirements of the formed complex for charge-state reduction during transition from solution to the gas phase. For Hg2+, the [PA-Q + Hg2+ + (PA-OH - H)-] ion was the largest observed species containing one Hg2+ ion. No 1:1 species ([PA-Q] or other degradation products:Hg2+) was observable. CONCLUSIONS ESI-MS/MS of complexes formed from PA-Q and transition metal ions is a formidable technique to probe initial formation of these complexes in solution. Previous work from other groups established structural requirements that enable charge-state reduction from Cu(II) to Cu(I) in ligand complexes during transition into the gas phase, and these rules allow us to propose structural features of PA-Q complexes with copper ions in solution. Copyright 2013 John Wiley & Sons, Ltd. Copyright
- Keller, Bernd O.,Esbata, Abdelhamid A.,Buncel, Erwin,Van Loon, Gary W.
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- Copper catalyzed aerobic oxidative amination of 3,4-dihydroquinoxalin-2(1H)-ones
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A copper catalyzed aerobic sp3 C[sbnd]H amination of 3,4-dihydroquinoxalin-2(1H)-ones is developed. This protocol provides a concise method to access 3-aminoquinoxalinone derivatives with good functional-group tolerances, utilizing primary and secondary aliphatic amines as nitrogen sources under mild and simple reaction conditions. It provides a practical approach to the synthesis of pharmaceutical active 3-aminoquinoxalinones.
- Wan, Shuocheng,Wang, Jie,Huo, Congde
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- Kinetics of solvolysis of 2-chloroquinoxaline
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Pseudo-first-order rate constants and activation parameters have been measured for the solvolysis of 2-chloroquinoxaline in various aquo-organic mixtures using methanol, ethanol, and isopropanol as the organic solvent. Excellent linear correlations are found between lnk and the mol fraction of cosolvent and In[H2O]. The medium effect on the rates of solvolysis is assessed by Grunwald-Winstein's mY correlationship. the estimated values of m (0.55-0.72) and the entropy of activation (148-212 J deg-1 mol-1) for the reactions are well in the range for a bimolecular aromatic substitution reactions.
- Patel
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- Electro-oxidative C-H azolation of quinoxalin-2(1H)-ones
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We have developed a practical, general protocol for direct C-H azolation reactions of quinoxalin-2(1H)-ones by electro-oxidative cross-coupling. These mild reactions proceed under metal-, oxidant-, and reagent-free conditions to provide synthetically useful azolated quinoxalin-2(1H)-ones. Furthermore, the reactions can be carried out with a pencil lead as an electrode and a 3 V battery as a power source, revealing the remarkable flexibility of this protocol.
- Ding, Ling,Hao, Yanke,Liu, Yuxiu,Niu, Kaikai,Song, Hongjian,Wang, Qingmin,Zhou, Pan
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- Synthesis and X-ray structures of unexpected 2-O-(5-deoxy-1,2-O- isopropylidene-α-D-glucofuranos-5-yloxy)quinoxalines
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Reaction of 3-methyl-2(1H)-quinoxalinone (4) and 2(1H)-quinoxalinone (5) with 5,6-anhydro-1,2-O-isopropylidene-α-D-glucofuranose 6 gives the unexpected O-glucoquinoxalines derivatives by the intermediary novel intramolecular rearrangement of 5,6-anhydro-1,2-O-isopropylidene-α-D- glucofuranose to the corresponding 3,6-anhydro form. The obtained O-glucoquinoxalines 7,8 were identified by NMR spectroscopy. The X-ray crystal structures have been determined at room temperature. Moreover, a solid-solid phase transition has been detected at 198.9 K for O-glucoquinoxalines 7 and the structure of the low-temperature phase has been solved at 188K.
- Jarmoumi, Chakir,Lakhrissi, Brahim,Mondieig, Denise,Negrier, Philippe,Leger,Massip,Lazard, Zhor,Benali, Bouziane,Massoui, Mohamed,Essassi, El Mokhtar
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- Multi-gram preparation of 7-nitroquinoxalin-2-amine
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Methodologies to obtain quinoxaline compounds regioselectively are rarely reported in literature, thus regioselective and multi-gram methodologies to obtain these derivatives are desirable to explore the entire potential of these scaffolds for academic and/or commercial application. A facile and multi-gram methodology is described to obtain compound 7-nitroquinoxalin-2-amine using o-phenylenediamine, a cheap and readily available reactant, as starting material in a five-step procedure in good yields and high purity without further purification such as crystallization or column chromatography.
- Do Amaral, Daniel N.,De Sá Alves, Fernando R.,Barreiro, Eliezer J.,Laufer, Stefan A.,Lima, Lídia M.
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- Dibenzothiophene Catabolism Proceeds via a Flavin-N5-oxide Intermediate
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The dibenzothiophene catabolic pathway converts dibenzothiophene to 2-hydroxybiphenyl and sulfite. The third step of the pathway, involving the conversion of dibenzothiophene sulfone to 2-(2-hydroxyphenyl)-benzenesulfinic acid, is catalyzed by a unique flavoenzyme DszA. Mechanistic studies on this reaction suggest that the C2 hydroperoxide of dibenzothiophene sulfone reacts with flavin to form a flavin-N5-oxide. The intermediacy of the flavin-N5-oxide was confirmed by LC-MS analysis, a co-elution experiment with chemically synthesized FMN-N5-oxide and 18O2 labeling studies.
- Adak, Sanjoy,Begley, Tadhg P.
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- Kinetics of the reaction of 2-chloro-quinoxaline with hydroxide ion in ACN-H2O and DMSO-H2O binary solvent mixtures
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The kinetics of alkaline hydrolysis of 2-chloroquinoxaline (QCl) with hydroxide ion was investigated spectrophotometrically at different percentages of aqueous-organic solvent mixtures with acetonitrile (10-60% v/v) and with dimethylesulphoxide (10-80%) over the temperature range from 25 to 45 °C. The reaction was performed under pseudo first order conditions with respect to 2-chloroquinoxaline (QCl). An increase in the percentage of organic solvent (v/v) has different effects on the reaction rate constants, presumably due to hydrogen bond donor and acceptor differences of the media and other solvatochromic parameters. The data were discussed in terms of the Kamelt-Taft parameter and ET(30). A nonlinear relation between the logarithm of the rate constant and reciprocal of the dielectric constant suggests the presence of selective solvation by the polar water molecules. Activation parameters δH#, δS# and δG# were determined and discussed. Springer Science+Business Media, LLC 2011.
- Fathalla, Magda F.
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- Micellar effects upon the alkaline hydrolysis of 2-(3-nitrophenoxy)quinoxaline. Effects of cationic head groups
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The rate of alkaline hydrolysis of the novel compound 2-(3-nitrophenoxy)quinoxaline 1 increases with increasing head group size in a series of cationic micellized surfactants (C16H33NR3Cl and C16H33NR3OH: R = Me, Et, n-Pr and n-Bu). The reactivity increase with increasing head group size is related to the disruption of the hydration of hydroxide ion.
- Cuenca, Angela
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- Oxidative removal of heterocyclic alkyl or sugar side chain by microwave: A simple step to xanthopterin, 6-formylpterin, and 3-hydroxymethyl-2(1H)- quinoxalinone
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One-step microwave-assisted oxidative removal of 3-methyl and 3-sugar side chain in 2(lH)-quinoxalinone system by selenium dioxide and sodium periodate respectively resulting 2(1H)quinoxalinone has been reported. Similarly xanthopterin (as acetyl derivative 11) was isolated from selenium dioxide oxidation of 7-methylxanthopterin. In the absence of adjacent lactam moiety, sodium periodate efficiently oxidizes 2-acetylaminopterin tetrols 7 and 8 to 2-acetylamino-6-formylpterin (16) and the quinoxaline tetrols 9 and 10 respectively to quinoxaline aldehyde 17. However, all the compounds remained unchanged on refluxing with selenium dioxide. The new quinoxalone compounds 15 and 18 were simply synthesized by manganese dioxide oxidation of the completely unprotected 3-substituted sugar of 2(lH)-quinoxalinone 5 and quinoxaline 10 respectively under microwave condition. Copyright
- Goswami, Shyamaprosad,Maity, Annada C.
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- Persulfate-promoted oxidative C-N bond coupling of quinoxalinones and: NH -sulfoximines
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The persulfate-meditated oxidative C-N bond coupling of the C-H bond of quinoxalinones and the N-H bond of NH-sulfoximines is reported. The reaction proceeds smoothly under transition metal-free conditions and provides good to excellent yields of sulfoximidoyl-functionalized quinoxalinone products under mild conditions. The optimized conditions were found to be suitable for a range of sulfoximine and quinoxalinone substrates. This reaction offers a new and convenient strategy to directly install the sulfoximine moiety into the C3 position of quinoxalinone.
- Sumunnee, Ladawan,Pimpasri, Chaleena,Noikham, Medena,Yotphan, Sirilata
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- Electro-oxidative C-H alkylation of quinoxalin-2(1: H)-ones with organoboron compounds
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Radical cleavage of C-B bonds to accomplish C-H functionalization is synthetically appealing but practically challenging. We report herein a mild electro-oxidative method for efficient C-H alkylation of quinoxalin-2(1H)-ones by means of radical addition reactions of alkyl boronic acids and esters and alkyl trifluoroborates to afford C-C coupled products. This journal is
- Niu, Kaikai,Hao, Yanke,Song, Lingyun,Liu, Yuxiu,Wang, Qingmin
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- Effect of colloidal self-assemblies on the basic hydrolysis of 2-(4-bromophenoxy)quinoxaline
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In the presence of cationic surfactants (C16H33NR3Cl; R = Me, n-Pr, n-Bu), the shape of rate versus surfactant concentration profiles for the basic hydrolysis of 2-(4-bromophenoxy)quinoxaline depends on substrate concentration. At low substrate concentration there is a single rate maximum and with a 10-fold substrate concentration increase a double rate maximum is observed. The first rate maximum is ascribed to reaction occurring in premicellar aggregates and the second to reaction in micelles. At low substrate concentration the effect of surfactant head group size was examined. Second-order rate constants in the micellar pseudophase increase with increasing head group size. Copyright
- Cuenca, Angela
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- Oxidative Cyclization-Induced Activation of a Phosphoinositide 3-Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics
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In this work, we designed a prodrug that reacts with cellular oxidative equivalents leading to ether cleavage and cyclization to release an active phosphatidylinositol 3-kinase (PI3K) inhibitor. We show that the compound reduces affinity for PI3KA relative to the PI3K inhibitor, is slow to intercellularly oxidize, and is resistant to liver microsomes. We observed modest activity in untreated acute myeloid leukemia cells and 14-fold selectivity relative to non-cancerous cells. The cellular activity of the compound can be modulated by the addition of antioxidants or oxidants, indicating the compound activity is sensitive to cellular reactive oxygen species (ROS) state. Co-treatment with cytosine arabinoside or doxorubicin was used to activate the compound inside cells. We observed strong synergistic activity specifically in acute myeloid leukemia (AML) cancer cells with an increase in selective anticancer activity of up to 90-fold. Thus, these new self-cyclizing compounds can be used to increase the selectivity of anticancer agents.
- Zhu, Haizhou,Mishra, Rosalin,Yuan, Long,Abdul Salam, Safnas F.,Liu, Jing,Gray, George,Sterling, Alyssa D.,Wunderlich, Mark,Landero-Figueroa, Julio,Garrett, Joan T.,Merino, Edward J.
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- Visible-light induced phosphonation of quinoxalines and quinoxalin-2(1H)-ones under aerobic metal-free conditions
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Phosphonation of quinoxalines and quinoxalin-2(1H)-ones utilizing aerobic oxygen as green oxidant under visible light conditions at room temperature has been described. Both quinoxalines and quinoxalin-2(1H)-ones are compatible with alkyl or aryl phosphonates and provided good yields of products through regioselective C-P bond formation under base/ligand-free conditions. Competitive experiments showed quinoxalin-2(1H)-ones are more reactive than quinoxalines under the present conditions, and the control experiments revealed the present transformation proceeds through a radical mechanism.
- Kumar, Rahul,Rawat, Deepa,Subbarayappa, Adimurthy
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- Metal-Free Direct Oxidative C?N Bond Coupling of Quinoxalin-2(1H)-ones with Azoles under Mild Conditions
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Direct C3?H amination of quinoxalin-2(1H)-ones with azoles under mild conditions promoted by PIFA has been achieved in good yield in a very fast manner. Mechanistic study revealed that the reaction proceeds through a radical process. In addition, this method could be applied to gram-scale reaction.
- Cai, Yuepiao,Du, Xinyue,Guo, Jingwen,Xia, Qinqin,Zhang, Lina,Zhang, Liting
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- 3-(Nitromethyl)-3,4-dihydroquinoxalin-2(1H)-ones: synthesis and structure
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[Figure not available: see fulltext.] Reactions of ethyl 3-nitroacrylate with o-phenylenediamine and its substituted derivatives were used for the synthesis of 3-(nitromethyl)-3,4-dihydroquinoxalin-2(1H)-ones, followed by structural characterization. Thes
- Pelipko, Vasilii V.,Makarenko, Sergey V.,Berestovitskaya, Valentina M.,Baichurin, Ruslan I.
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- Visible-Light-Promoted Switchable Synthesis of C-3-Functionalized Quinoxalin-2(1H)-ones
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A visible-light-promoted synthesis of quinoxalin-2(1H)-ones has been developed using 9-mesityl-10-methylacridinium perchlorate as an organo-photocatalyst. The atmosphere-controlled method (Ar/air) enabled the selective synthesis of hydroxyl- and acyl-containing quinoxalin-2(1H)-ones under mild reaction conditions without the use of any metal catalysts or toxic reagents. A fluorescent labelling experiment showed that hydroxyl-containing quinoxalin-2(1H)-ones may have utility in various biological applications as potent fluorophores. (Figure presented.).
- Aganda, Kim Christopher C.,Hong, Boseok,Lee, Anna
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- PIDA-induced oxidative C–N bond coupling of quinoxalinones and azoles
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A metal-free promoted direct oxidative C–N bond coupling of quinoxalinones and azoles for the rapid and effective synthesis of potent pharmaceutical important 3-(azol-1-yl)quinoxalin-2-one has been developed. Employing PIDA as the easily available mediator, the desired coupling products were isolated in moderate to excellent yields with a good substrate scope under operational simplicity and mild reaction conditions. Preliminary mechanistic studies suggested that a radical process is likely to be involved in the reaction.
- Wimonsong, Watchara,Yotphan, Sirilata
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- Design and synthesis of new quinoxaline derivatives as anticancer agents and apoptotic inducers
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The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds VIId, VIIIa, VIIIc, VIIIe and XVa exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound VIIIc induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound VIIIc could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line.
- El Newahie, Aliya M.S.,Nissan, Yassin M.,Ismail, Nasser S.M.,Abou El Ella, Dalal A.,Khojah, Sohair M.,Abouzid, Khaled A.M.
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- Synthesis of 2-(2-nitrophenoxy)quinoxaline and its basic hydrolysis in aqueous solutions of non-reactive counter-ion surfactants with bulky head groups
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The synthesis of the novel compound 2-(2-nitrophenoxy)quinoxaline (2) is described and its basic hydrolysis was studied in the presence of non-reactive counter-ion surfactants with different head group size. Micellar effects upon the reaction of OH- with (2) were analyzed by using a mass-action-like equation.
- Cuenca, Angela,Strubinger, Adelitza
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- A Computer-Driven Scaffold-Hopping Approach Generating New PTP1B Inhibitors from the Pyrrolo[1,2-a]quinoxaline Core
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Protein tyrosine phosphatase 1B (PTP1B) is a very promising target for the treatment of metabolic disorders such as type II diabetes mellitus. Although it was validated as a promising target for this disease more than 30 years ago, as yet there is no drug in advanced clinical trials, and its biochemical mechanism and functions are still being studied. In the present study, based on our experience generating PTP1B inhibitors, we have developed and implemented a scaffold-hopping approach to vary the pyrrole ring of the pyrrolo[1,2-a]quinoxaline core, supported by extensive computational techniques aimed to explain the molecular interaction with PTP1B. Using a combination of docking, molecular dynamics and end-point free-energy calculations, we have rationally designed a hypothesis for new PTP1B inhibitors, supporting their recognition mechanism at a molecular level. After the design phase, we were able to easily synthesize proposed candidates and their evaluation against PTP1B was found to be in good concordance with our predictions. Moreover, the best candidates exhibited glucose uptake increments in cellulo model, thus confirming their utility for PTP1B inhibition and validating this approach for inhibitors design and molecules thus obtained.
- García-Marín, Javier,Griera, Mercedes,Alajarín, Ramón,Rodríguez-Puyol, Manuel,Rodríguez-Puyol, Diego,Vaquero, Juan J.
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- Redox-activated, hypoxia-selective DNA cleavage by quinoxaline 1,4-di-N-oxide
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Quinoxaline 1,4-dioxide (4) is the historical prototype for modern heterocyclic N-oxide antitumor agen s such as 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, 1) and 3-amino-2-quinoxalinecarbonitrile 1,4-dioxide (11). Early experiments in bacterial cell lines suggested that enzymatic, single-electron reduction of quinoxaline 1,4-dioxides under low-oxygen (hypoxic) conditions leads to DNA damage. Here the ability of quinoxaline 1,4-dioxide to cleave DNA has been explicitly characerized using in vitro assays. The hypoxia-selective DNA-cleaving properties of 4 reported here may provide a chemical basis for understanding the cytotoxic and mutagenic activities of various quinoxaline 1,4-dioxide antibiotics. Copyright
- Ganley, Brian,Chowdhury, Goutam,Bhansali, Jennifer,Daniels,Gates, Kent S.
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- One-pot multicomponent synthesis of novel 2-(piperazin-1-yl) quinoxaline and benzimidazole derivatives, using a novel sulfamic acid functionalized Fe3O4 MNPs as highly effective nanocatalyst
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The immobilization of sulfonic acid on the surface of Fe3O4 magnetic nanoparticles (MNPs) as a novel acid nanocatalyst has been successfully reported. The morphological features, thermal stability, magnetic properties, and other physicochemical properties of the prepared superparamagnetic core–shell (Fe3O4@PFBA–Metformin@SO3H) were thoroughly characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), thermogravimetric analysis–differential thermal analysis (TGA-DTA), atomic force microscopy (AFM), dynamic light scattering (DLS), Brunauer–Emmett–Teller (BET), and vibrating sample magnetometer (VSM) techniques. It was applied as an efficient and reusable catalyst for the synthesis of 2-(piperazin-1-yl) quinoxaline and benzimidazole derivatives via a one-pot multiple-component cascade reaction under green conditions. The results displayed the excellent catalytic activity of Fe3O4@PFBA–metformin@SO3H as an organic–inorganic hybrid nanocatalyst in condensation and multicomponent Mannich-type reactions. The easy separation, simple workup, excellent stability, and reusability of the nanocatalyst and quantitative yields of products and short reaction time are some outstanding advantages of this protocol.
- Esam, Zohreh,Akhavan, Malihe,Bekhradnia, Ahmadreza
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- Decarboxylative Hydroxylation of Benzoic Acids
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Herein, we report the first decarboxylative hydroxylation to synthesize phenols from benzoic acids at 35 °C via photoinduced ligand-to-metal charge transfer (LMCT)-enabled radical decarboxylative carbometalation. The aromatic decarboxylative hydroxylation is synthetically promising due to its mild conditions, broad substrate scope, and late-stage applications.
- Ritter, Tobias,Su, Wanqi,Xu, Peng
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p. 24012 - 24017
(2021/10/06)
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- Visible-Light-Induced Cycloaddition of α-Ketoacylsilanes with Imines: Facile Access to β-Lactams
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We report the synthesis of β-lactams from α-ketoacylsilanes and imines, which proceeds via a formal [2+2] photochemical cycloaddition with in situ generation of siloxyketene. This mild and operationally simple reaction proceeds in an atom-economic fashion with broad substrate scope, including aldimines, ketimines, hydrazones, and fused nitrogen heterocycles, affording a variety of important β-lactams with satisfactory diastereoselectivities in most cases. This reaction also features good functional-group tolerance, facile scalability and product diversification. Experimental and computational studies suggest that α-ketoacylsilanes can serve as photochemical precursors by engaging in a 1,3 silicon shift to the distal carbonyl group.
- Ye, Jian-Heng,Bellotti, Peter,Paulisch, Tiffany O.,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 13671 - 13676
(2021/05/11)
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- Electrochemical chlorination and bromination of electron-deficient C[sbnd]H bonds in quinones, coumarins, quinoxalines and 1,3-diketones
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The electrochemistry-promoted chlorination and bromination of electron-deficient C[sbnd]H bonds was developed, using quinones, coumarins, quinoxalines and 1,3-diketones. This protocol features readily available and safe halogen sources (hydrochloric acid and KBr), high site-selectivity and mild reaction conditions. It could provide an efficient access to a series of chlorinated and brominated quinones, coumarins, quinoxalines and 1,3-diketones.
- Yu, Dan,Ji, Ruixue,Sun, Zhihui,Li, Wenjie,Liu, Zhong-Quan
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supporting information
(2021/11/16)
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- C?H Methylation of Iminoamido Heterocycles with Sulfur Ylides**
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The direct methylation of N-heterocycles is an important transformation for the advancement of pharmaceuticals, agrochemicals, functional materials, and other chemical entities. Herein, the unprecedented C(sp2)-H methylation of iminoamido heterocycles as nucleoside base analogues is described. Notably, trimethylsulfoxonium salt was employed as a methylating agent under aqueous conditions. A wide substrate scope and excellent level of functional-group tolerance were attained. Moreover, this method can be readily applied to the site-selective methylation of azauracil nucleosides. The feasibility of gram-scale reactions and various transformations of the products highlight the synthetic potential of the developed method. Combined deuterium-labeling experiments aided the elucidation of a plausible reaction mechanism.
- Ghosh, Prithwish,Kwon, Na Yeon,Kim, Saegun,Han, Sangil,Lee, Suk Hun,An, Won,Mishra, Neeraj Kumar,Han, Soo Bong,Kim, In Su
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supporting information
p. 191 - 196
(2020/10/29)
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- Simple and green synthesis of benzimidazoles and pyrrolo[1,2-: A] quinoxalines via Mamedov heterocycle rearrangement
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A method for the synthesis of coupling compounds of benzimidazoles and pyrrolo[1,2-a]quinoxalines via Mamedov Heterocycle Rearrangement is reported here. This method was conducted at room temperature and only solvent (HOAc) was required. A series of 4-(1H-benzo[d]imidazol-2-yl)pyrrolo[1,2-a]quinoxaline derivatives were obtained in moderate to good yields.
- Li, Shichen,Feng, Lei,Ma, Chen
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supporting information
p. 9320 - 9323
(2021/06/14)
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- K2S2O8-catalyzed highly regioselective amidoalkylation of diverse N-heteroaromatics in water under visible light irradiation
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A K2S2O8-catalyzed versatile C(sp2)-C(sp3) bond formation with N-heteroaromatics and γ-lactams/amides was developed. Quinoxalin-2(1H)-one, quinoline, isoquinoline, phthalazine, and benzothiazole reacted with γ-lactams/amides to give the corresponding C(sp2)-H amidoalkylation products in moderate to good yields with high regioselectivity. This visible-light-induced photocatalyst-free reaction was conducted in H2O at ambient temperature, which comply with the principles of "green chemistry". The new K2S2O8 catalytic mechanism was investigated with control experiments.
- Chen, Zhi,Li, Jianjun,Ren, Quanlei,Song, Shengjie,Wang, Chaodong,Xu, Ning,Zhou, Jiadi
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supporting information
p. 5753 - 5758
(2021/08/23)
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- Rapid alkenylation of quinoxalin-2(1H)-ones enabled by the sequential Mannich-type reaction and solar photocatalysis
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Herein, a rapid alkenylation of quinoxalin-2(1H)-ones enabled by a combination of Mannich-type reaction and solar photocatalysis is demonstrated. A wide range of functional groups are compatible, affording the corresponding products in moderate-to-good yields. Control experiments illustrate that the in situ generated 1O2 plays a central role in this reaction. This green and efficient strategy provides a practical solution for the synthesis of potentially bioactive compounds that containing a 3,4-dihydroquinoxalin-2(1H)-one structure.
- Huang, Lin,Xu, Jun,He, Lei,Liang, Chenfeng,Ouyang, Yani,Yu, Yongping,Li, Wanmei,Zhang, Pengfei
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supporting information
p. 3627 - 3631
(2021/05/03)
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- Direct functionalization of quinoxalin-2(1H)-one with alkanes: C(sp2)-H/C(sp3)-H cross coupling in transition metal-free mode
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Considering the significance of pharmaceutically important heterocycles, efficient and highly versatile protocols for the functionalization of diverse heterocycles with easily accessible feedstock are crucial. Here, we have reported selective alkylation of quinoxalin-2(1H)-one with a broad class of hydrocarbons having different C(sp3)-H bonds with varying bond strengths using di-tert-butyl peroxide (DTBP) as an alkoxyl radical mediator for hydrogen atom transfer (HAT). This dehydrogenative coupling approach utilizes feedstock chemicals such as cycloalkanes, cyclic ethers and alkyl arenes as coupling partners. This protocol exhibits good functional group compatibility and selectivity regarding both heterocycles and unactivated alkanes. Moreover, this methodology allows functionalization of relatively strong C-H bonds of adamantane and exclusive selectivity towards 3° C(sp3)-H bonds is observed. We also illustrate the applicability of this C(sp2)-H/C(sp3)-H cross-coupling for practical access to bioactive pharmaceuticals.
- Dagar, Neha,Raha Roy, Sudipta,Singh, Swati
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p. 5383 - 5394
(2021/06/28)
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- Visible Light-Promoted Radical Relay Cyclization/C-C Bond Formation of N-Allylbromodifluoroacetamides with Quinoxalin-2(1 H)-ones
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A visible light-promoted radical relay of N-allylbromodifluoroacetamide with quinoxalin-2(1H)-ones was developed in which 5-exo-trig cyclization and C-C bond formation were involved. This protocol was performed under mild conditions to facilely offer a variety of hybrid molecules bearing both quinoxalin-2(1H)-one and 3,3-difluoro-γ-lactam motifs. These prepared novel skeletons would expand the accessible chemical space for structurally complex heterocycles with potential biological activities.
- Ye, Zhi-Peng,Liu, Fang,Duan, Xin-Yu,Gao, Jie,Guan, Jian-Ping,Xiao, Jun-An,Xiang, Hao-Yue,Chen, Kai,Yang, Hua
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p. 17173 - 17183
(2021/11/18)
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- Palladium-catalyzed direct Hiyama arylation of quinoxalin-2(1H)-ones with aryl siloxanes in water
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An efficient method for palladium-catalyzed direct Hiyama coupling of various quinoxalin-2(1H)-ones with aryl siloxanes has been developed. The protocol provides a convenient access to a variety of useful C3-arylated 1-methylquinoxalin-2(1H)-one derivatives in reasonable yields by using low cost water as a solvent and oxygen as an oxidant.
- Liu, Xinya,Liu, Zhenwei,Xue, Yingying,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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- Multifunctional quinoxaline-hydrazone derivatives with acetylcholinesterase and monoamine oxidases inhibitory activities as potential agents against Alzheimer’s disease
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Multitarget molecules are considered as an effective way for the treatment of AD, instead of the classic one-drug-one-target strategy because of the multifactorial nature of AD. A variety of studies indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted quinoxaline-hydrazone derivatives were synthesized, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity and MAOA/B inhibitory activity. Based on the experimental results, compound 5l exhibited good inhibitory potency on both AchE (IC50 = 0.028 ± 0.001 μM) and monoamine oxidase B (IC50 = 0.046 ± 0.002 μM). Molecular modeling studies showed that 5l could bind to the active site of AChE and MAO-B. Taken together, these results suggested that compound 5l might be a potential multifunctional agent for the treatment of AD.
- Ilgin, Sinem,Karaduman, Abdullah Burak,Levent, Serkan,Osmaniye, Derya,?avu?o?lu, Betül Kaya,?evik, Ulviye Acar,?zkay, Yusuf,Kaplancikli, Zafer As?m,Karaburun, Ahmet ?a?r?,Sa?lik, Begüm Nurpelin,Turan, Gülhan
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p. 1000 - 1011
(2020/04/29)
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- Synthetic method 1 -benzyl -3 -alkyl quinoxaline -2 (1H)-ketone (by machine translation)
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The invention relates to a synthetic method of 1 - benzyl -3 -alkyl quinoxaline -2 (1H)-ketone, wherein 1 - benzylquinoxaline -2 (1H)-ketone and phenyl iodine (III) dicarboxylic acid ester 1:2-1 are added into an organic solvent to obtain an organic phase which is washed, dried, concentrated under reduced pressure, petroleum ether-ethyl acetate and ethyl acetate. 2.5 (1H)-one. ?timetimebase and ethyl acetate are used to obtain the organic phase, and the reaction mixture is extracted with ethyl acetate-water mixed solution to obtain an organic phase which is a 1 -benzyl -3 - alkylquinoxaline -2-one. The method is simple in process, convenient to operate and high in product yield. (by machine translation)
- -
-
Paragraph 0024; 0026; 0029; 0030; 0032-0033
(2020/10/04)
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- Electrochemical decarboxylative C3 alkylation of quinoxalin-2(1: H)-ones with N -hydroxyphthalimide esters
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We have developed a protocol for electrochemical decarboxylative C3 alkylation of a wide range of quinoxalin-2(1H)-ones under metal- and additive-free conditions. N-Hydroxyphthalimide esters derived from chain, cyclic, primary, secondary, and tertiary carboxylic acids with a broad scope proved to be suitable substrates. This operationally simple protocol performed in an undivided cell under constant-current conditions is suitable for late-stage functionalization of quinoxalin-2(1H)-ones. The reactions can even be carried out with a 3 V battery as a power source, which demonstrates that organic electrosynthesis can be accomplished without the need for specialized equipment.
- Niu, Kaikai,Song, Lingyun,Hao, Yanke,Liu, Yuxiu,Wang, Qingmin
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supporting information
p. 11673 - 11676
(2020/10/20)
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- A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones
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An enantioselective photooxidative Mannich reaction of dihydroquinoxalinones with ketones by the merger of organophotoredox and asymmetric organocatalysis is described. This protocol features very mild reaction conditions using simple and cheap catalysts (Eosin Y and (S)-Proline) for the synthesis of chiral quinoxaline derivatives with good to high yields (up to 94%) and excellent enantioselectivities (up to 99% ee).
- Rostoll-Berenguer, Jaume,Blay, Gonzalo,Mu?oz, M. Carmen,Pedro, José R.,Vila, Carlos
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supporting information
p. 6011 - 6015
(2019/08/26)
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- TRI-SUBSTITUTED IMIDAZOLES FOR THE INHIBITION OF TGF BETA AND METHODS OF TREATMENT
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Pharmaceutical compounds, their methods of manufacture, and methods of treatment of mammals with pharmaceutical compounds are provided.
- -
-
Paragraph 0092
(2019/01/17)
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- Construction of C(sp2)?C(sp3) Bond between Quinoxalin-2(1H)-ones and N-Hydroxyphthalimide Esters via Photocatalytic Decarboxylative Coupling
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A novel visible-light-driven decarboxylative coupling of alkyl N-hydroxyphthalimide esters (NHP esters) with quinoxalin-2(1H)-ones has been developed. This C(sp2)?C(sp3) bond-forming transformation exhibits excellent substrate generality with respect to both the coupling partners. Of note, a series of 3-primary alkyl-substituted quinoxalin-2(1H)-ones that were difficult to synthesize by previous methods could be obtained in moderate to excellent yields. Additionally, the mild conditions, easy availability of substrates, wide functional group tolerance and operational simplicity make this protocol practical in the synthesis of 3-alkylated quinoxalin-2(1H)-ones.
- Yan, Zhiyang,Sun, Bin,Zhang, Xun,Zhuang, Xiaohui,Yang, Jin,Su, Weike,Jin, Can
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p. 3344 - 3349
(2019/09/06)
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- Substituted phosphorylated quinolone 3- derivative as well as preparation method and application thereof (by machine translation)
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The invention discloses a substituted phosphorylated quinolone 3 - derivative with a structure shown in the specification. Each substituent defines a detailed description. Compared with a traditional preparation 3 - method, the substituted phosphorylated quinolone derivative disclosed 3 - by the invention has the advantages of simple and easily available raw materials, mild reaction conditions, avoidance of participation of transition metals and oxidant, further responding to the commercialization cost of the quinolinone derivatives, and laying a foundation for industrial production of the quinolinone derivatives. (by machine translation)
- -
-
Paragraph 0045-0046
(2019/11/28)
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- Electrochemical Cross-Coupling of C(sp2)?H with Aryldiazonium Salts via a Paired Electrolysis: an Alternative to Visible Light Photoredox-Based Approach
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Photoredox-based C?H bond functionalization constitutes one of the most powerful and atom-economical approaches to organic syntheses. During this type of reaction, single electron transfer takes place between the photocatalyst (PC) and redox- active substrates. Electrosynthesis also involves electron transfer between substrates and electrodes. In this paper, we focus upon electrochemical cross-coupling of C(sp2)?H with aryldiazonium salts and have developed an efficient electrochemical approach to the Minisci-type arylation reaction. The constant current paired electrosynthesis proceeds in a simple undivided cell without external supporting electrolyte, features a wide range of substrates and is easy to scale-up. These results demonstrate that photoredox-based cross-coupling of C(sp2)?H with aryldiazonium salts can also proceed successfully under paired electrolysis conditions, thereby contributing to understanding of the parallels between photosynthesis and electrosynthesis. (Figure presented.).
- Jiang, Yang-ye,Dou, Gui-yuan,Zhang, Luo-sha,Xu, Kun,Little, R. Daniel,Zeng, Cheng-chu
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supporting information
p. 5170 - 5175
(2019/11/13)
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- Nickel-catalyzed electrochemical reductive decarboxylative coupling of: N -hydroxyphthalimide esters with quinoxalinones
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Herein the first example of electrochemically enabled, NiCl2-catalyzed reductive decarboxylative coupling of N-hydroxyphthalimide (NHP) esters with quinoxalinones is reported. A range of primary, secondary, tertiary aliphatic carboxylic acids and amino acid-derived esters were tolerated well. This decarboxylative coupling allows access to structurally diverse 3-alkylated quinoxalinones in up to 91% yields.
- Lian, Fei,Xu, Kun,Meng, Wei,Zhang, Haonan,Tan, Zhoumei,Zeng, Chengchu
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supporting information
p. 14685 - 14688
(2019/12/11)
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- Visible-light-induced C(sp3)-H activation for a C-C bond forming reaction of 3,4-dihydroquinoxalin-2(1: H)-one with nucleophiles using oxygen with a photoredox catalyst or under catalyst-free conditions
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A convenient photocatalyzed oxidative coupling reaction of 4-alkyl-3,4-dihydroquinoxalin-2(1H)-one and its derivatives with a variety of nucleophiles was developed with a ruthenium photoredox catalyst and oxygen under a household compact fluorescent light. With a slower reaction rate, the cross coupling transformation can be achieved in the absence of an external photocatalyst with a similar isolated yield. An application to the synthesis of natural product cephalandole A was also demonstrated.
- Akula, Pavan Sudheer,Hong, Bor-Cherng,Lee, Gene-Hsiang
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p. 19580 - 19584
(2018/06/11)
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- Rationalization of benzazole-2-carboxylate versus benzazine-3-one/ benzazine-2,3-dione selectivity switch during cyclocondensation of 2-aminothiophenols/phenols/anilines with 1,2-biselectrophiles in aqueous medium
-
The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via the 5-endo-trig process contrary to Baldwin's rule. On the other hand, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via the 6-exo-trig process in compliance with Baldwin's rule. The mechanistic insights of these cyclocondensation reactions using the hard-soft acid-base principle, quantum chemical calculations (density functional theory), and orbital interaction studies rationalize the selectivity switch of benzothiazole-2-carboxylates versus benzazine-3-ones/ benzazine-2,3-diones. The presence of water facilitates these cyclocondensation reactions by lowering of the energy barrier.
- Dhameliya, Tejas M.,Chourasiya, Sumit S.,Mishra, Eshan,Jadhavar, Pradeep S.,Bharatam, Prasad V.,Chakraborti, Asit K.
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p. 10077 - 10091
(2018/05/31)
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- Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof
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The present invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.
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Page/Page column 355; 356
(2016/04/26)
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- COMBINATION OF KINASE INHIBITORS AND USES THEREOF
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The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.
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Page/Page column 73
(2015/02/19)
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- Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold
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In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a series of new quinoxaline-based derivatives was designed and synthesized. The target compounds were biologically evaluated for their inhibitory activity against VEGFR-2. The design of the target compounds was accomplished after a profound study of the structure activity relationship (SAR) of type-II VEGFR-2 inhibitors. Among the synthesized compounds, 1-(2-((4-methoxyphenyl)amino)-3- oxo-3,4 dihydroquinoxalin-6-yl)-3-phenylurea (VIIa) displayed the highest inhibitory activity against VEGFR-2. Molecular modeling study involving molecular docking and field alignment was implemented to interpret the variable inhibitory activity of the newly synthesized compounds.
- Shahin, Mai I.,Abou El Ella, Dalal A.,Ismail, Nasser S.M.,Abouzid, Khaled A.M.
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- COMBINATION OF KINASE INHIBITORS AND USES THEREOF
-
The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3 -kinase α and/or mTOR in a subject.
- -
-
Paragraph 00641
(2014/10/04)
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- Palladium(II)-catalyzed oxidative arylation of quinoxalin-2(1 H)-ones with arylboronic acids
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A straightforward palladium-catalyzed oxidative C-3 arylation of quinoxalin-2(1H)-ones with arylboronic acids is reported. This protocol is compatible with a wide range of functional groups and allows construction of various biologically important quinoxalin-2(1H)-one backbones.
- Carrer, Amandine,Brion, Jean-Daniel,Messaoudi, Samir,Alami, Mouad
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supporting information
p. 5606 - 5609
(2013/11/19)
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- Design, synthesis, and preliminary in vitro and in vivo pharmacological evaluation of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl] phenyl}thiazoles as atypical antipsychotic agents
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A series of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl] phenyl} thiazoles were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were designed, synthesized, and characterized by spectral data (IR, 1H NMR, and MS) and the purity was ascertained by microanalysis. The D2 and 5-HT2A affinity of the synthesized compounds was screened in vitro by radioligand displacement assays on membrane homogenates isolated from rat striatum and rat cortex, respectively. Furthermore, all the synthesized final compounds (10a-g; 11a-g; 12a-g) were screened for their in vivo pharmacological activity in Swiss albino mice. D2 antagonism studies were performed using climbing mouse assay model and 5-HT2A antagonism studies were performed using quipazine-induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy and 12d, 11f, and 10a were found to be the most active compounds with 5-HT2A/D2 ratio of 1.23077, 1.14286, and 1.12857, respectively, while the standard drug risperidone exhibited 5-HT2A/D2 ratio of 1.0989. Among the twenty one new chemical entities, three compounds (12d, 11f, and 10a) were found to exhibit better atypical antipsychotic activity as they were found to have higher Meltzer index than the standard drug risperidone.
- Chandra Sekhar, Kondapalli Venkata Gowri,Rao, Vajja Sambasiva,Deuther-Conrad, Winnie,Sridhar, Divya,Nagesh, Hunsur Nagendra,Kumar, Vellas Sreedhar,Brust, Peter,Kumar, Muthyala Murali Krishna
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p. 1660 - 1673
(2013/07/26)
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- SUBSTITUTED AMINOQUINOXALINES AS TYROSINE THREONINE KINASE INHIBITORS
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The present invention relates to substituted aminoquinoxaline compounds of general formula (I) in which (II), R2, R3, R4, R6, R7, n and m are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.
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Page/Page column 56
(2011/04/14)
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