- 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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- 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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- 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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p. 1874 - 1878
(2017/09/02)
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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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supporting information
p. 6424 - 6426
(2016/06/09)
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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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- 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 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.
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Paragraph 00641
(2014/10/04)
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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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p. 1319 - 1328
(2013/07/28)
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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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- 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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experimental part
p. 1258 - 1270
(2012/06/18)
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- Pyrrolopyrrole cyanine dyes: A new class of near-Infrared dyes and fluorophores
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Pyrrolopyrrole cyanine (PPCy) dyes are presented as a novel class of near-infrared (NIR) chromophores, which are synthesized in a condensation reaction of diketopyrrolopyr-role with heteroarylacetonitrile compounds. Their optical properties are marked by strong and narrow-band NIR absorptions. Complexation prod-ucts with BF2 and BPh2 show strong NIR fluorescence and hardly any ab-sorption in the visible range. We syn-thesized a series of new PPCys that differ only in the heterocyclic peripheral groups of the chromophore. With this strategy, the absorption spectra can be tuned between 684 and 864 nm, while high fluorescence quantum yields are maintained. The influence of the heterocycle on the optical properties of the dyes is discussed.
- Fischer, Georg M.,Isomaki-Krondahl, Magnus,Gottker-Schnetmann, Inigo,Daltrozzo, Ewald,Zumbusch, Andreas
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supporting information; experimental part
p. 4857 - 4864
(2009/12/08)
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- Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A
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A urea class of high affinity niacin receptor agonists was discovered. Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin.
- Shen, Hong C.,Szymonifka, Michael J.,Kharbanda, Divya,Deng, Qiaolin,Carballo-Jane, Ester,Wu, Kenneth K.,Wu, Tsuei-Ju,Cheng, Kang,Ren, Ning,Cai, Tian-Quan,Taggart, Andrew K.,Wang, Junying,Tong, Xinchun,Waters, M. Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
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p. 6723 - 6728
(2008/04/03)
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- Imidazoquinoxaline protein tyrosine kinase inhibitors
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Novel imidazoquinoxalines and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic disorders.
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- Imidazoquinoxaline protein tyrosine kinase inhibitors
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Novel imidazoquinoxalines and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic disorders.
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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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p. 2395 - 2401
(2007/10/03)
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- MCR IX: A new and easy way for the preparation of piperazine-2-keto-3- carboxamides
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Piperazine-2-keto-3-carboxamides (5) are formed by an one-pot U-4CR (Ugi four component reaction) between ethylenediamine (1), glyoxylic acid- hemiacetal (2), a carboxylic acid (3) and an isocyanide (4).
- Zychlinski, Alexander V,Ugi, Ivar
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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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p. 545 - 550
(2007/10/02)
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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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p. 403 - 406
(2007/10/03)
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- Structure and Stereochemistry of cis-Dihydro Diol and Phenol Metabolites of Bicyclic Azaarenes from Pseudomonas putida UV4
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Biotransformation of quinoline, isoquinoline, quinoxaline and quinazoline using growing cultures of Pseudomonas putida UV4 yielded cis-dihydro diols from the oxidation of the carbocyclic aromatic ring.Aromatic hydroxylation was observed in both carbocyclic and heterocyclic rings.Ring cleavage of the quinoline skeleton to yield anthranilic acid, and cis-diol formation (with alkene bond reduction) to yield cis-5,6,7,8-tetrahydroquinazoline-5,6-diol from quinazoline were observed.The cis-dihydro diol metabolites of quinoline (5,6- and 7,8-) and quinoxaline (5,6-) were found to be optically pure, while metabolism of isoquinoline gave on e homochiral (5,6-) and one racemic 7,8-) cis-dihydro diol product.The absolute configuration of the cis-dihydro diol metabolites have been determined using 1H NMR analyses, stereochemical correlations and X-ray crystallography methods.
- Boyd, Derek R.,Sharma, Narain D.,Dorrity, Michael R. J.,Hand, Mark V.,McMordie, R. Austin S.,et al.
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p. 1065 - 1072
(2007/10/02)
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- Process for producing 2-hydroxyquinoxaline derivatives
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A process for producing a 2-hydroxyquinoxaline which may be substituted with one or more substituents selected from the group consisting of halogen, lower alkyl and lower alkoxy, which comprises reacting o-phenylenediamine which may be substituted with one or more substituents selected from the group consisting of halogen, lower alkyl and lower alkoxy with glyoxylic acid in a lower aliphatic alcohol solvent without using a catalyst is disclosed. By the process according to the present invention, the 2-hydroxyquinoxaline derivatives can be obtained at a high purity and a high yield without using any catalyst.
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- AN UNEXPECTED RING-OPENING IN THE REISSERT REACTION ON 2,3-DIPHENYLQUINOXALINE-N-OXIDE.
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When quinoxaline-N-oxide 1 is reacted with KCN and benzoyl chloride in water (the Reissert reaction) or methanol, the products are 2-, 5- and 6- chloroquinoxaline (the latter being the major product: 42+/-6percent) and small amounts of 2-cyanoquinoxaline.Using three equivalents of trimethylsilyl cyanide instead of KCN, and dichloromethane as the solvent, leads to a 72percent yield of 2-cyanoquinoxaline.The reaction of trimethylsilyl cyanide and benzoyl chloride with 2,3-diphenylquinoxaline-N-oxide 2 leads to an unexpected ring-opening product 13; its structure is based on spectroscopic data and on an X-ray crystallographic analysis.
- Nasielski, J.,Heilporn, S.,Nasielski-Hinkens, R.,Tinant, B.,Declercq, J. P.
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p. 7795 - 7804
(2007/10/02)
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- Synthesis and aldose reductase inhibitory activity of N-1,N-4-disubstituted 3,4-dihydro-2(1H)-quinoxalinone derivatives
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Synthetic routes have been developed for the preparation of 4-acylated, 4-benzenesulfonylated, and 4-methylated 3,4-dihydro-2(1H)-quinoxalinone-1-acetic acids. One example of the corresponding propionic acid has also been made. These compounds have been evaluated for their ability to inhibit bovine lens aldose reductase in vitro. Some members from this series also show weak activity in vivo, inhibiting sorbitol formation in sciatic nerves of streptozotocin-diabetic rats.
- Sarges,Lyga
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p. 1475 - 1479
(2007/10/02)
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- DEGRADATIONS OF 1-METHYL-3-BENZENESULFONYLOXYALLOXAZINE BY NUCLEOPHILIC REAGENTS
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Degradation of 1-methyl-3-benzenesulfonyloxyalloxazine by nucleophilic reagents produced derivatives of 2-hydrazino-3-quinoxalinecarboxylic acid and anhydro-1-hydroxy-3-methyl-s-triazolo-quinoxalinium hydroxide.
- Hamby, James M.,Bauer, Ludwig
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- A Comparison of Nucleophilic Reactions of 3-Benzenesulfonyloxyalloxazine and its 1-Methyl Analog.
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Reactions of 3-benzenesulfonyloxyalloxazine (1a) and its 1-methyl analog 1b with a number of nucleophilic reagents are reported.Relatively small nucleophiles, such as hydroxide ion, methanol, ethanol, methylamine, hydrazine and hydroxylamine converted 1a to 4-carboxy-s-triazoloquinoxalin-1(2H)-ones and the corresponding esters or amides.As the size of the amine increased from methylamine to ethylamine, dimethylamine, propylamine and isopropylamine, there were obtained 4-(carboxamido)-s-triazoloquinoxalin-1(2H)-ones, (1-carboxamido)imidazoloquinoxalines and 2,3-bis(ureido)quinoxalines.Sodium hydride or potassium cyanide in hot DMF degraded 1a to imidazoloquinoxaline.However, methylmercaptide and benzylmercaptide ions attacked the sulfonate group of 1a to form 3-hydroxyalloxazine. 1-Methyl-3-benzenesulfonyloxyalloxazine (1b) reacted with methanol, ethanol, 1-propanol, and to some degree 2-propanol, in the presence of triethylamine to furnish anhydro-1-hydroxy-3-methyl-4-(alkoxycarbonyl)-s-triazoloquinoxalinium hydroxides.However, sodium methoxide in methanol converted this starting material to a mixture of anhydro-1-hydroxy-3-methyl-s-triazoloquinoxalinium hydroxide and 1-methyl-3-hydroxyflavazole.A saturated aqueous solution of triethylamine transformed 1b to anhydro-1-hydroxy-3-methyl-s-triazoloquinoxalinium hydroxide, apparently via the corresponding unstable 4-carboxylic acid.The reactions of 1b with a number of aliphatic amines yielded either amides based on the above mesionic system or on the 3-carboxamido-2-quinoxalyl semicarbazide structure.The reaction of 1b with potassium cyanide furnished 1-methylimidazoloquinoxaline.Mechanisms to explain all of the degradations are advanced.
- Hamby, James M.,Bauer, Ludwig
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p. 1013 - 1024
(2007/10/02)
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- Metabolism of Bicyclic Aza-arenes by Pseudomonas putida to Yield Vicinal cis-Dihydrodiols and Phenols
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Metabolism of the aza-arenes quinoline, isoquinoline, quinazoline, and quinoxaline by a mutant strain of the bacterium Pseudomonas putida resulted in attack at the carbocyclic ring (to yield stable cis-dihydrodiols and phenols) and at the heterocyclic ring (to yield phenols and ring cleavage products).
- Boyd, Derek R.,McMordie, R. Austin S.,Porter, H. Patricia,Dalton, Howard,Jenkins, Richard O.,Howarth, Oliver W.
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p. 1722 - 1724
(2007/10/02)
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- Preparation of 2-hydroxyquinoxaline
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An improved procedure for the manufacture of 2-hydroxyquinoxalines from reacting a dialkyl tartrate with a periodate, adjusting the pH of the resulting reaction mixture, and condensing said mixture with an o-phenylenediamine.
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- OXIDATION OF SOME HETARYLHYDRAZINES WITH SELENIUM DIOXIDE
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The oxidation of 2-benzimidazolyl- and 2-quinoxalinylhydrazines with selenium dioxide in hydrochloric acid in the presence of cuprous chloride leads to the formation of 2-chloro derivatives of the heterocycles.When the reaction is carried out in ethanol, 2-benzimidazolylhydrazines give symmetrical formazans.In both cases oxidation proceeds through a step involving the formation of hetarenediazonium salts.
- Sedov, Yu. A.
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p. 217 - 220
(2007/10/02)
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