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A general protocol for the palladium-catalyzed dearomative trimethylenemethane [3+2] cycloaddition reaction with simple nitroarene substrates is described. This methodology leads to the exclusive formation of the dearomatized alicyclic products without subsequent rearomatization. The reaction is tolerant toward a broad range of heterocyclic and benzenoid substrates. The use of chiral bisdiamidophosphite ligands enabled the development of an enantioselective variant of this transformation, representing one of the rare examples of an asymmetric catalytic dearomatization process.

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Quinoxaline – Wikipedia,
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A general protocol for the palladium-catalyzed dearomative trimethylenemethane [3+2] cycloaddition reaction with simple nitroarene substrates is described. This methodology leads to the exclusive formation of the dearomatized alicyclic products without subsequent rearomatization. The reaction is tolerant toward a broad range of heterocyclic and benzenoid substrates. The use of chiral bisdiamidophosphite ligands enabled the development of an enantioselective variant of this transformation, representing one of the rare examples of an asymmetric catalytic dearomatization process.

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Selective fluorination of a range of pyridine and quinoline substrates to give corresponding 2-fluoro-derivatives can be readily achieved in high yield at room temperature using elemental fluorine-iodine mixtures. Reaction of fluorine with iodine forms, in situ, systems that function like sources of both iodonium and fluoride ions and fluorination of heterocyclic derivatives is suggested to proceed by fluoride ion attack on intermediate W-iodo-heterocyclic species. Quinoxaline derivatives react under similar conditions to give either the 2-fluoro- or 2,3-difluoro-quinoxaline derivatives depending on the ratio of fluorine passed through the solution. In related processes, pyridine can be alkoxylated upon reaction of an appropriate alcohol and fluorine.

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There is provided a compound having Formula (I) R1-Z-R2 Formula (I) wherein R1 is an optionally substituted phenyl ring; R2 is or comprises an optionally substituted aromatic ring; and Z is -X-Y-L- or -Y-X-L- wherein either X is selected from -S(=O)(=O)- and -C(=O)-, and Y is -NR3-; or X is selected from -S(=O)(=O)- and -S-, and Y is -C(R4)(R5)-; L is an optional linker; and R3, R4 and R5 are each independently selected from H and hydrocarbyl; and wherein when R2 comprises the following structural moiety, Formula (II) wherein Q is an atom selected from the group consisting of S, O, N and C; the compound is selected from compounds of the formulae R1-C(=O)-NR3-L-R2; R1-S(=O)(=O)-C(R4)(R5)-L-R2; R1-S-C(R4)(R5)-L-R2; R1-NR3-S(=O)(=O)-L-R2; R1-NR3-C(=O)-L-R2; R1-C(R4)(R5)-S(=O)(=O)-L-R2; and R1-C(R4)(R5)-S-L-R2. These compounds are useful as 11beta-hydroxysteriod dehydrogenase inhibitors in the treatment of i.a. diabetes.

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There is provided a compound having Formula (I) R1-Z-R2 Formula (I) wherein R1 is an optionally substituted phenyl ring; R2 is or comprises an optionally substituted aromatic ring; and Z is -X-Y-L- or -Y-X-L- wherein either X is selected from -S(=O)(=O)- and -C(=O)-, and Y is -NR3-; or X is selected from -S(=O)(=O)- and -S-, and Y is -C(R4)(R5)-; L is an optional linker; and R3, R4 and R5 are each independently selected from H and hydrocarbyl; and wherein when R2 comprises the following structural moiety, Formula (II) wherein Q is an atom selected from the group consisting of S, O, N and C; the compound is selected from compounds of the formulae R1-C(=O)-NR3-L-R2; R1-S(=O)(=O)-C(R4)(R5)-L-R2; R1-S-C(R4)(R5)-L-R2; R1-NR3-S(=O)(=O)-L-R2; R1-NR3-C(=O)-L-R2; R1-C(R4)(R5)-S(=O)(=O)-L-R2; and R1-C(R4)(R5)-S-L-R2. These compounds are useful as 11beta-hydroxysteriod dehydrogenase inhibitors in the treatment of i.a. diabetes.

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Parkinson disease is a neurodegenerative disorder of aging, characterized by disabling motor symptoms resulting from the loss of midbrain dopaminergic neurons and the decrease of dopamine in the striatum. Current therapies are directed at treating the symptoms but there is presently no cure for the disease. In order to discover neuroprotective compounds with a therapeutical potential, our research team has established original and highly regioselective methods for the synthesis of 2,3-disubstituted 6-aminoquinoxalines. To evaluate the neuroprotective activity of these molecules, we used midbrain cultures and various experimental conditions that promote dopaminergic cell loss. Among a series of 11 molecules, only compound MPAQ (2-methyl-3-phenyl-6-aminoquinoxaline) afforded substantial protection in a paradigm where dopaminergic neurons die spontaneously and progressively as they mature. Prediction of blood-brain barrier permeation by Quantitative Structure-Activity Relationship studies (QSARs) suggested that MPAQ was able to reach the brain parenchyma with sufficient efficacy. HPLC-MS/MS quantification in brain homogenates and MALDI-TOF mass spectrometry imaging on brain tissue sections performed in MPAQ-treated mice allowed us to confirm this prediction and to demonstrate, by MALDI-TOF mass spectrometry imaging, that MPAQ was localized in areas containing vulnerable neurons and/or their terminals. Of interest, MPAQ also rescued dopaminergic neurons, which (i) acquired dependency on the trophic peptide GDNF for their survival or (ii) underwent oxidative stress-mediated insults mediated by catalytically active iron. In summary, MPAQ possesses an interesting pharmacological profile as it penetrates the brain parenchyma and counteracts mechanisms possibly contributive to dopaminergic cell death in Parkinson disease.

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Nano-TiO2 as an eco-friendly and efficient nanocatalyst was applied for quinoxaline preparation with improved yield. In this protocol, diketones and 1,2-diamines were condensed in the presence of catalyst at room temperature.

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We report the preparation of novel 1,4,8-triazaphenanthrenes and show that the target compounds are efficiently obtained from the corresponding 6-aminoquinoxalines after N-propargylation followed by copper-catalyzed 6-endo-dig cycloisomerization and aromatization. The cyclization was found to be completely regioselective.

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The invention relates to the use of compounds corresponding to formula (I) STR1 in which one of the substituents R1 or R2 is a nitro group while the other is hydrogen, halogen, an amino group, a mono- or dialkylamino group containing C1-4 alkyl groups, a C1-4 alkyl or alkoxy group, R3 and R4 independently of one another represent hydrogen or a C1-4 alkyl group, A is a >CHR6 – or a >C=O- group, where R6 is hydrogen or a C1-4 alkyl group, and R5 is hydrogen or a C1-4 alkyl group, or salts thereof as substantive dyes in hair-dyeing compositions. When the substituent groups in formula I represent one of the combinations I-IV shown in the table below, the compounds are novel and are useful in hair-dyeing compositions. ______________________________________R1 R2 R3 R4 R5 A______________________________________I: H NO2 H CH3 H CH2II: H NO2 CH3 CH3 H CH2III: NH2 NO2 H H H CH2IV: H NO2 H H CH3 CH2.______________________________________

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The present invention relates to compounds of Formula (I) below, to their pharmaceutically acceptable salts and to their isomers or mixtures of isomers: HetAr?X?CHR1R2 (I) in which: -HetAr represents a group chosen from: ?X represents a linear, saturated or unsaturated, hydrocarbon-based chain comprising from 8 to 22 carbon atoms, optionally interrupted by an ?NH? or ?NH?CO? group, ?R1 represents a hydrogen atom or an ?OH, ?O(C1-C6)alkyl, ?OCO((C1-C6)alkyl), ?OSO2((C1-C6)alkyl) or ?OSO3H group, and ?R2 represents a hydrogen atom or a (C2-C6)alkynyl, (C2-C6)alkenyl or (C3-C6)cycloalkyl group. The present invention also relates to a process for preparing the compounds of Formula (I), and also to the use thereof, especially in the treatment of neurodegenerative diseases.

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