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A class of N-(naphthalen-1-yl)-N?-alkyl oxalamides have been proven to be powerful ligands, making a coupling reaction of (hetero)aryl iodides with primary amines proceed at 50 C with only 0.01 mol % of Cu2O and ligand as well as a coupling reaction of (hetero)aryl bromides with primary amines and ammonia at 80 C with only 0.1 mol % of Cu2O and ligand. A wide range of coupling partners work well under these conditions, thereby providing an easy to operate method for preparing (hetero)aryl amines.

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Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo

The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties. Lead compounds were selected based on potency in a cellular screen and physicochemical properties. Among these, 12 had good aqueous solubility, permeability and long-term solid-state stability at 23 C. Compound 12 also displayed comparable or better efficacy in cellular assays relative to SFN and had in vivo activity in a mouse cigarette smoke challenge model of acute oxidative stress.

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Identification of a Novel 1,4,8-Triazaphenanthrene Derivative as a Neuroprotectant for Dopamine Neurons Vulnerable in Parkinson’s Disease

Parkinson’s disease (PD) is a chronic degenerative disorder characterized by typical motor symptoms caused by the death of dopamine (DA) neurons in the midbrain and ensuing shortage of DA in the striatum, at the level of nerve terminals. No curative treatment is presently available for PD in clinical practice. In our search for neuroprotectants in PD, we generated new 1,4,8-triazaphenanthrenes by combining 6-endo-dig-cycloisomerization of propargylquinoxalines and Suzuki or Sonogashira cross-coupling reactions. Neuroprotection assessment of newly synthesized 1,4,8-triazaphenanthrenes in a PD cellular model resulted in the discovery of a new hit compound PPQ (5m). Neuroprotection by 5m was concentration-dependent and the result of a combined effect on intracellular calcium release channels and astroglial cells. Of interest, 5m also counteracted DA cell loss in a mouse model of PD, making this molecule a promising candidate for PD treatment.

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HETEROCYCLIC CARBOXYLIC ACID AMIDE LIGAND AND APPLICATIONS THEREOF IN COPPER CATALYZED COUPLING REACTION OF ARYL HALOGENO SUBSTITUTE

Provided are a heterocyclic carboxylic acid amide ligand and applications thereof in a copper catalyzed coupling reaction. Specifically, provided are uses of a compound represented by formula (I), definitions of radical groups being described in the specifications. The compound represented by formula (I) can be used as the ligand in the copper catalyzed coupling reaction of the aryl halogeno substitute, and is used or catalyzing the coupling reaction for forming the aryl halogeno substitute having C?N, C?O, C?S and other bonds.

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METHODS FOR USING (2-IMIDAZOLIN-2-YLAMINO) QUINOXALINE DERIVATIVES

A method of treating a mammal comprises administering to a mammal an effective amount to provide a desired therapeutic effect in the mammal of a compound selected from the group consisting of those having the formula: STR1 ,pharmaceutically acceptable acid addition salts thereof and mixtures thereof, wherein R 1 and R 4 are independently selected from the group consisting of H and alkyl radicals having 1 to 4 carbon atoms; the R 2 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the R 3 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the 2-imidazolin-2-ylamino group may be in any of the 5-, 6, 7-or 8-positions of the quinoxaline nucleus; and R 5, R 6 and R 7 each is located in one of the remaining 5-, 6-, 7-or 8-positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals having 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide desired therapeutic effects, such as reduction in peripheral pain, anesthetization of the central nervous system, constriction of one or more blood vessels, reduction in or prevention of at least one effect of ischemia, decongestion of one or more nasal passages, and reduction of at least one effect of an inflammatory disorder.

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THIOPHENE DERIVATIVES FOR THE TREATMENT OF DISORDERS CAUSED BY IGE

Thiophene derivatives of formula (I) and a pharmaceutically acceptable salt thereof are provided. These compounds have utility for the treatment or prevention of disorders caused by IgE, such as allergy, type 1 hypersensitivity or familiar sinus inflammation.

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Methods of preventing and reducing the severity of stress-associated conditions

The present invention provides a method of preventing or reducing the severity of a stress-associated condition in a subject by systemically administering to the subject an effective amount of brimonidine or a pharmaceutically acceptable salt, ester, amide, sterioisomer or racemic mixture thereof. Stress-associated conditions that can be treated according to a method of the invention include, but are not limited to, dyspepsia, tachycardias other than tachycardia associated with myocardial ischemia, panic attack, non-inflammatory dermatogical conditions, disorders of muscle contraction, sensory hypersensitivity associated with migraine, and behavioral disorders.

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Redox-active poly(6-(1H-pyrrol-1-yl)quinoxaline) as a novel organic anode material for aqueous hybrid flow batteries

To develop efficient electrochemical energy storage systems for large-scale use of renewable energy, a novel quinoxaline-bearing redox-active conjugated polymer (poly(6-(1H-pyrrol-1-yl)quinoxaline), PPyQX) has been synthesized via a facile bromine oxidation polymerization approach and employed as electro-active anode material for aqueous hybrid flow batteries. The PPyQX displays a quasi-reversible redox reaction at ?0.79 V vs the standard hydrogen electrode (SHE) with good stability in aqueous alkaline electrolytes. An aqueous hybrid flow battery is fabricated using the PPyQX as the anode material and K4Fe(CN)6 as the catholyte, respectively, which displays an open circuit potential of 1.15 V at 50% state of charge (SOC) and a discharge capacity of 67.1 mAh g?1 at the current density of 1 A g?1. The maximum power density reaches 2.7 and 1.5 W g?1 at 100% and 50% SOC, respectively. After 1000 charge-discharge cycles, ca. 74.8% of initial discharge capacity is retained, projecting an average capacity retention rate of ~99.975% per cycle. The coulombic efficiency is near to 93.8% and the round-trip energy efficiency is kept around 80.5%.

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Fluorescent sensing of anions using a bis-quinoxaline amidothiourea based supramolecular cleft; an example of an anion-induced deprotonation event

The quinoxaline 1, possessing a 2,6-pyridyl-based amidothiourea moiety, with the view of forming a pre-organised molecular cleft, was developed as a fluorescent anion sensor. The sensing ability of 1 was evaluated in organic solution where both the ground and the excited state of 1 was affected upon recognition of anions such as acetate [as tetrabutylammonium salt (TBAAc) solution] at the amiodothiourea moieties in MeCN. The fluorescence of 1, with lambdamax at 477 nm, was, on all occasions quenched, upon anion recognition. Using TBAOH, we also show that the same anion-induced changes occurred; demonstrating that for this particular sensor, the anion-sensing takes place via a deprotonation mechanism. This anion-induced deprotonation event was further investigated by carrying out 1H NMR titrations on 1, using both AcO- and OH- in DMSO-d6.

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6- endo -dig Cycloisomerization of N -Propargyl Aminoquinoxalines: A New Route to 1,4,8-Triazaphenanthrenes

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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