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Whole-cell recordings were used to study the antagonist pharmacology of two subtypes of non-N-methyl-D-aspartate glutamate receptors: the kainate-preferring subtype expressed by rat dorsal root ganglion (DRG) neurons and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring subtype expressed by neurons from rat cerebral cortex. A series of quinoxaline derivatives were tested for the ability to distinguish between AMPA and kainate receptors, as determined by differential potency. Of the nine compounds studied, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) snowed the highest selectivity for AMPA-preferring receptors, whereas 5-chloro-7-trifluoromethyl-2,3-quinoxalinedione (ACEA-1011) showed the highest selectivity for the kainate-preferring subtype. NBQX blocked non-N-methyl-D-aspartate currents in cortical cells with a Kb of 0.3 muM, but in DRG neurons the Kb for NBQX was 3-fold higher (0.9 muM). ACEA-1011 also blocked the currents in DRG cells with a Kb of ?1 muM, but in cortical neurons the Kb for this drug was 10-12 muM. Several additional compounds were tested for selective potency, including 5-nitro-6,7,8,9-tetrahydrobenzo[G]indole-2,3-dione-3-oxime, gamma-D-glutamylaminomethylsulphonic acid, and derivatives of kynurenic acid and 1-benzazepine. 5-Nitro-6,7,8,9-tetrahydrobenzo[G]indole-2,3-dione-3-oxime displayed the highest selectivity in this group, blocking kainate receptors with a Kb of 6 muM while inhibiting AMPA receptors with a Kb of >100 muM. The remaining antagonists showed <3-fold selectivity between AMPA and kainate receptor subtypes. Our results suggest that most competitive antagonists block native AMPA and kainate receptors with approximately similar potencies, which is in marked contrast to the substantial differences in potency that have been observed with receptor agonists. The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 15804-19-0 is helpful to your research. Related Products of 15804-19-0

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Quinoxaline – Wikipedia,
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Three new alpha,alpha?-diimine ligands were synthesized based on condensation of 1,10-phenanthroline-5,6-dione with 1,2-phenylenediamine derivatives using different approaches. All compounds were fully characterized by IR, 1H and 13C NMR, UV-visible, and MS spectroscopies. We report the first example of a dipyrido[3,2-f:2?,3?-h]quinoxalino[2,3-b]quinoxaline, which exhibits a strong absorption at 430 nm and an interesting electrochemical behavior. These new molecules may have biological potential and are of synthetic and technological importance.

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The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds present in, e.g., coffee. Also, the invention relates to the discovery of specific compounds and compositions containing that function as bitter taste blockers and the use thereof as bitter taste blockers or flavor modulators in, e.g., coffee and coffee flavored foods, beverages and medicaments. Also, the present invention relates to the discovery of a compound that antagonizes numerous different human T2Rs and the use thereof in assays and as a bitter taste blocker in compositions for ingestion by humans and animals.

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The present invention relates to compounds of Formula I or II, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: 1 which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

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Histone lysine demethylases (KDMs) have drawn much attention as targets of therapeutic agents. KDM5 proteins, which are Fe(II)/alpha-ketoglutarate-dependent demethylases, are associated with oncogenesis and drug resistance in cancer cells, and KDM5-selective inhibitors are expected to be anticancer drugs. However, few cell-active KDM5 inhibitors have been reported and there is an obvious need to discover more. In this study, we pursued the identification of highly potent and cell-active KDM5-selective inhibitors. Based on the reported KDM5 inhibitors, we designed several compounds by strategically merging two fragments for competitive inhibition with alpha-ketoglutarate and for KDM5-selective inhibition. Among them, compounds 10 and 13, which have a 3-cyano pyrazolo[1,5-a]pyrimidin-7-one scaffold, exhibited strong KDM5-inhibitory activity and significant KDM5 selectivity. In cellular assays using human lung cancer cell line A549, 10 and 13 increased the levels of trimethylated lysine 4 on histone H3, which is a specific substrate of KDM5s, and induced growth inhibition of A549 cells. These results should provide a basis for the development of cell-active KDM5 inhibitors to highlight the validity of our inhibitor-based fragment merging strategy.

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Compounds and compositions are disclosed, which are useful as inhibitors of acetyltransferase Eis, a mediator of kanamycin resistance in Mycobacterium tuberculosis.

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A number of new symmetrically and asymmetrically 2,3-disubstituted quinoxalines were synthesized through functionalization of 2,3-dichloroquinoxaline (2,3-DCQ) with a variety of sulfur and/or nitrogen nucleophiles. The structures of the obtained compounds were established based on their spectral data and elemental analysis. The antimicrobial activity for the prepared compounds was investigated against four bacterial species and two fungal strains. The symmetrically disubstituted quinoxalines 2, 3, 4, and 5 displayed the most significant antibacterial activity, while compounds 6a, 6b, and the pentacyclic compound 10 showed considerable antifungal activity. Furthermore, compounds 3f, 6b showed broad antimicrobial spectrum against most of the tested strains.

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The reaction of 2,3-dichloroquinoxaline (1) with various acid hydrazides (II) in 1:2 mole ratio using HMPT as solvent gives the corresponding ditriazoloquinoxalines (IV) in excellent yields while equimolar quantities of I and II react together in acetonitrile/K2CO3 under PTC conditions to form the respective oxadiazinoquinoxalines (V) as exclusive reaction products in good yields.The reaction mechanisms and spectral data of IV and V are also reported.

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Self-assembly-based molecular structures have proven to be highly relevant to the development of soft materials. This work reports the synthesis, thermal behavior and computational analysis of two novel heterocyclic compounds with a non-symmetrical shape bearing a single long alkyl (C12) chain. The compounds 2-(4-dodecyloxy-phenyl)-1H-benzoimidazole, 1, with three-ring core mesogen with a more linear shape, and 1-dodecyl-1,4-dihydro-quinoxaline-2,3-dione, 2, with a condensed two-ring core with a more compact discotic shape, were obtained in good yields and investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC) analysis. Benzimidazole derivative 1 was found to present liquid crystalline property, with a mesophase range from 85 to 177 C, as verified by POM and DSC, with a smectogenic polymorphism assigned as a SmB and a more organized unidentified SmX phase. On the other hand, although quinoxaline 2 did not show liquid crystal behavior, POM analysis indicated an interesting spherulitic packing pattern, typical of a columnar arrangement of the molecules by possible H-bond interactions. Computational results indicated that combining intermolecular hydrogen bonds and hydrophobic interactions lead to a non-planar lamellar model for benzimidazole 1, consistent with the smectic packing found in the liquid crystalline phase and a twist-type packing for compound 2, which is consistent with a spherulitic model.

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2,3(1H,4H)-quinoxalinediones of the formula I STR1 where R1 is hydrogen, an aliphatic radical which has up to 12 carbons and can be substituted by one of the following: phenyl, cyclopentyl, cyclohexyl or –CO–R3, –CO–O–R3 or –CO–NH–R3, where R3 is hydrogen, C1 -C4 -alkyl, phenyl, benzyl or 1-phenylethyl, a cycloaliphatic radical with up to 12 carbons or phenyl, where the cyclic groups in R1 can have up to three of the following substituents: C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy, halogen, nitro, cyano, –CO–O–R3 and –CO–NH–R3 ; R2 is 1-pyrrolyl which can have up to two of the following substituents: C1 -C4 -alkyl, phenyl, phenylsulfonyl, nitro, cyano and –CO–O–R3, –CO–NH–R3, –CH2 –O–R3, –O–R3 and –CH=NO–R3 R radicals are identical or different and are the following: C1 -C4 -alkyl, C1 -C4 -alkoxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, trichloromethoxy, fluorine, chlorine, bromine, iodine, nitro, cyano and –CO–O–R3 and –CO–NH–R3 as well as a fused-on benzene ring; n is 0-3, and 2,3(1H,4H)-quinoxalinediones I’ STR2 where R1 has the stated meanings, are suitable as drugs in the treatment of neurodegenerative disorders and neurotoxic disturbances of the central nervous system.

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Quinoxaline – Wikipedia,
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