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Based on the principle that the nitro-group can quench the fluorescence and can be reduced under hypoxic conditions, several novel nitroheterocyclic compounds without 2-nitroimidazole as potential hypoxic markers were prepared. Although they were synthesized from the same matrix, nitrosubstituted acenaphtho[1,2-b]quinoxaline, these compounds exhibited quite different fluorescence changes when they were differently nitrosubstituted. Their evaluation for imaging tumor hypoxia was carried out in V79 cells in vitro by Fluorescence Microplate Reader. After 3.5 h, the hypoxic-oxic fluorescence differential incubated with A1, A4, and A5 in V79 cells could reach 6, 9, and 11 times differential fluorescence between oxic and hypoxic cells separately, which are suitable for further evaluation as probes for hypoxic cells in tumors in vivo.

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5- and 6-Nitroquinoxalines and some of their derivatives are aminated in a liquid ammonia solution of potassium permanganate to yield the corresponding 2- and/or 3- and/or 5-amino compounds.Quantum-chemical calculations are made to explain the regioselectivity of the amination reactions. Key Words: Amination / Nitroquinoxalines / Reactivity indices / Calculations, MNDO / Quinoxalines

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Quinoxalino[2,3-b?]porphyrins are pi-expanded porphyrins, having a quinoxaline fused to a beta,beta?-pyrrolic position of the porphyrin. They are used as components in systems proposed as ‘molecular wires’. Knowledge of their redox properties is of value in the design of electron- or hole-conduction systems. In particular, the location of the charge density in the radical anions of quinoxalinoporphyrins can be modulated by peripheral functionalization. New theoretical treatments of electrochemical potentials are developed that identify the site of reduction in both the anions and the dianions of 33 quinoxalinoporphyrins. These molecules include free-base and metallated macrocycles substituted on the quinoxaline with electron-withdrawing groups (NO2, Cl, Br) and/or electron-donating groups (NH2, OCH3). Spectroelectrochemistry, density-functional theory calculations, and substituent-parameter models are used to verify the analysis. Five distinct patterns are observed for the locations of the first and second reductions; some of these patterns involve delocalized charges. Nitroquinoxalinoporphyrins with the nitro groups at the 5- and 6-quinoxaline positions are found to have quite different properties owing to distortions caused by peri interactions that force the nitro group of the 5-nitro regioisomer out of conjugation. Charge localization on the nitroquinoxaline fragment is found for some molecules, and this is attributed to ion-pairing with the 0.1 M tetrabutylammonium perchlorate electrolyte used, leading to the verified prediction that electron-paramagnetic resonance spectra of these molecules taken without the electrolyte yield delocalized anions. These properties enable the control of conduction through molecular wires synthesised from quinoxalinoporphyrins. the Owner Societies.

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The present invention relates to a compound of formula: (I) or a pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing a viral infection such as HIV using the same.

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(Chemical Equation Presented) 1,4-Diethyl-1,2,3,4-tetrahydro-6- nitroquinoxaline 4 was synthesized by alkylative reduction of 6-nitroquinoxaline. Catalytic reduction of 4 followed by cyclocondensation with heterocyclic malondialdehydes afforded novel 8-(heteroaryl)-1,4-diethyl-1,2,3,4- tetrahydropyrido[2,3-g]quinoxalines. The solutions of these novel compounds having 1,4-diethyl-1,2,3,4-tetrahydroquinoxaline framework as an electron releasing system showed absorption in the range of 424-426 nm in the visible region and exhibited brilliant bluish-green fluorescence. The thermogravimetric curve obtained by thermogravimetric analysis displayed that these fluorophores possess excellent thermal stability with one-step thermal decomposition.

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Solutions of nitramine and nitrate ester explosives and model compounds were thermolyzed at various hydrostatic pressures and their rates of decomposition were measured.The effects of pressure on their rates were used to infer the mechanism of their initial decomposition steps.Most nitramines, including the explosive octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), appear to undergo homolysis of the N-NO2 bond, because their reaction rates decrease with increasing pressure.Exceptions are hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and the model compound, 6-nitro-1,2-dinitroso-1,2,3,4-tetrahydroquinoxaline, which react faster with increasing pressure.These two compounds can aromatize by elimination of HNO2 and HNO, respectively.Secondary nitrate esters shift their major decomposition pathway from homolysis of the O-NO2 bond to elimination of HNO3 in the pressure range of 0.4 to 0.8 GPa.The elimination reaction resembles carboxylate ester pyrolysis with E1 character.

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An efficient and selective one-pot two-step method, for the synthesis of quinoxalines by oxidative coupling of vicinal diols with 1,2-phenylenediamine derivatives, has been developed by using gold nanoparticles supported on nanoparticulated ceria (Au/CeO2) or hydrotalcite (Au/HT) as catalysts and air as oxidant, in the absence of any homogeneous base. Reaction kinetics shows that the reaction controlling step is the oxidation of the diol to alpha-hydroxycarbonyl compound. Furthermore, a one-pot three-step synthesis of 2-methylquinoxaline starting from 1,2-dinitrobenzene and 1,2-propanediol has been successfully carried out with 98% conversion and 83% global yield to the final product.

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The carbanion of chloromethyl aryl sulfone reacts with 1-Cyanonaphthalene to form a bis-annulated product whereas with 1-nitronaphthalene vicarious nucleophilic substitution of hydrogen takes place.This result and the bis-annulation of quinoxalines and naphthyridines which was reported earlier are rationalized in terms of the negative charge delocalization in the intermediate ?-adducts.

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Plasmodium falciparum thioredoxin reductase (PfTrxR: NADPH + Trx(S) 2 + H+ ? NADP+ + Trx(SH)2) is a high Mr flavin-dependent TrxR that reduces thioredoxin (Trx) via a CysXXXXCys pair located penultimately to the C-terminal Gly. In this respect, PfTrxR differs significantly from its human counterpart which bears a Cys-Sec redox pair at the same position. PfTrxR is essentially involved in antioxidant defense and redox regulation of the parasite and has been previously validated by knock-out studies as a potential drug target for malaria chemotherapy. Moreover, human TrxR is present in most cancer cells at levels tenfold higher than in normal cells. Here we report the discovery of a series of potent inhibitors of PfTrxR. The three most promising inhibitors, 3 (IC50PfTrxR=2muMandIC50hTrxR=50muM), 7 (IC50PfTrxR=2muMandIC50hTrxR= 140muM), and 11 (IC50PfTrxR=0.5muMandIC50hTrxR=4muM) were selective for the parasite enzyme. Detailed mechanistic characterization of the effects of these compounds on the PfTrxR-catalyzed reaction showed clear uncompetitive inhibition with respect to both substrate and cofactor. For the most specific PfTrxR inhibitor 7, an alkylation mechanism study based on a thiol conjugation model was performed. Furthermore, all three compounds were active in the lower micromolar range on the chloroquine-resistant P. falciparum strain K1 in vitro.

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6-nitro-, 2-methyl-6-nitro- and 2,3-dimethyl-6-nitroquinoxaline have been transformed into their N-oxides by MCPBA in chloroform; the nitro group orients the oxygen atom preferentially to nitrogen atom N1, but the N4:N1 selectivity is diminished in the methylated derivatives.Under the action of POCl3 (the Meisenheimer reaction), the N-oxides of the unmethylated compounds are transformed into chloro-nitroquinoxalines having lost the N-oxide oxygen atom.The orientation of the entering chloride ion is discussed on the basis of electronic effects induced by the N-oxide and nitro groups, and it is suggested that the last step, the elimination of “HPO2Cl2” is a concerted process.

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