Chemical Properties and Facts of 6-Nitroquinoxaline-2,3-dione

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Derivatives of the nonselective excitatory amino acid antagonist kynurenic acid (4-oxo-1,4-dihydroquinoline-2-carboxylic acid, 1) have been synthesized and evaluated for in vitro antagonist activity at the excitatory amino acid receptors sensitive to N-methyl-D-aspartic acid (NMDA), quisqualic acid (QUIS or AMPA), and kainic acid (KA). Introduction of substituents at the 5-, 7-, and 5,7-positions resulted in analogues having selective NMDA antagonist action, as a result of blockade of the glycine modulatory (or coagonist) site on the NMDA receptor. Regression analysis suggested a requirement for optimally sized, hydrophobic 5- and 7-substituents, with bulk tolerance being greater at the 5-position. Optimization led to the 5-iodo-7-chloro derivative (53), which is the most potent and selective glycine/NMDA antagonist to date (IC50 vs [3H]glycine binding, 32 nM; IC50’s for other excitatory amino acid receptor sites, >100 muM). Substitution of 1 at the 6-position resulted in compounds having selective non-NMDA antagonism and 8-substituted compounds were inactive at all receptors. The retention of glycine/NMDA antagonist activity in heterocyclic ring modified analogues, such as the oxanilide 69 and the 2-carboxybenzimidazole 70, suggests that the 4-oxo tautomer of 1 and its derivatives is required for activity. Structurally related quinoxaline-2,3-diones are also glycine/NMDA antagonists, but are not selective and are less potent than the 1 derivatives, and additionally show different structure-activity requirements for aromatic ring substitution. On the basis of these results, a model accounting for glycine receptor binding of the 1 derived antagonists is proposed, comprising (a) size-limited, hydrophobic binding of the benzene ring, (b) hydrogen-bond acceptance by the 4-oxo group, (c) hydrogen-bond donation by the 1-amino group, and (d) a Coulombic attraction of the 2-carboxylate. The model can also account for the binding of quinoxaline-2,3-diones, quinoxalic acids, and 2-carboxybenzimidazoles.

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Quinoxaline – Wikipedia,
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Chemical Properties and Facts of 15804-19-0

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The synthesis, single-crystal X-ray structure and magnetic properties of [Cu3L2Cl2(DMF)4]n (1), where L2- is the 2,3-dioxyquinoxalinate(-2) ligand, are reported. The complex was prepared by the reaction of CuCl2 and 1,4-dihydro-2,3-quinoxalinedione (H2L?) under basic conditions using either solvothermal or normal laboratory techniques. Compound 1 is a 3D coordination polymer with an (82.10)-a, lig (LiGe) topology, containing the ligand in a novel 3.1111 (Harris notation) coordination mode. Variable-temperature and variable-field magnetic studies reveal that the ligand L2- propagates weak antiferromagnetic exchange interactions through its “quinoxaline” part. IR data are discussed in terms of the structural features of 1 and the coordination mode of L2-.

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Now Is The Time For You To Know The Truth About 18671-97-1

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Compounds and pharmaceutically acceptable salts thereof of Formula I are disclosed. Certain compounds and salts of Formula I are active as CMA modulators. The disclosure provides pharmaceutical compositions containing a compound of Formula I.

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Something interesting about 55687-05-3

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2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469) is among the most highly and broadly active antitumor agents to have been evaluated in our laboratories and is currently scheduled to enter clinical trials in 2001. The mechanism or mechanisms of action of XK469 remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogues of XK469 and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions – I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety – to determine the resultant in vitro and in vivo effects of chemical alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of XK469 showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-{4-[(2-quinoxalinyl)oxy]phenoxy}propionic acid, generated the most highly and broadly active antitumor agents. A methyl, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of 1 was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of XK469 (region III), i.e., CONH2, CONHCH3, CON(CH3)2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.

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The Absolute Best Science Experiment for 7-Bromo-1-methyl-1H-quinoxalin-2-one

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The first example of oxidative C-H fluoroalkoxylation of quinoxalinones with fluoroalkyl alcohols under transition-metal and solvent-free conditions is described. This approach provides the synthesis of fluoroalkoxylated quinoxaline derivatives with good to excellent yields under mild reactions conditions. This method can also be extended to the facile and efficient synthesis of histamine-4 receptor.

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New explortion of 15804-19-0

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Some new quinoxaline-6-sulfonamide and phthalazine-6-sulfonamide derivatives were synthesized. The majority of the prepared compounds showed antibacterial activity.

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Discover the magic of the 49679-45-0

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Chlorination of ethyl(quinoxalin-2(1 H)one)-3-carboxylate 1 gave ethyl (2-chloroquinoxaline)-3-carboxylate 2;thionation of 1 by P2S5 or 2 by thiourea yielded the same product 3.Reaction of chloro compound 2 or thiocompound 3 with hydrazine hydrate gave pyrazolylquinoxaline 4. The reaction of ester 1 with thiourea or hydrazine hydrate afforded pyrimidoquinoxaline 5 or carbohydrazide 6; the reaction of 6 with carbon disulfide in basic medium followed by alkylation afforded oxadiazoloquinoxaline derivatives 7, 8a, b. Carboazide 9 was produced by reaction of 5 with nitrous acid. Compound 9 on heating in an inert solvent, with or without amines, in alcohols or hydrolysis in H2O undergoes Curtius rearrangments to yield 10-13.Reaction of 13 with thiosemicarbazide gave triazoloquinoxaline 14 which on reaction with alkylhalides or hydrazine hydrate yielded 15a-c while hydrolysis of 13 gave 3-aminoquinoxalinone 16 which was used as an intermediate to produce 17-20.

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Something interesting about 2,3-Dichloroquinoxaline

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A trifluoroacetic acid promoted step-economical one-pot approach to the synthesis of furo-fused quinoxalines/pyrazines by the reaction of 2,3-dichloroquinoxalines/pyrazines with alkynes is described. The reaction involves a selective in-situ Sonogashira coupling step and a hydroxylation followed by a metal-free 5-endo-dig cyclization. Preliminary experiments show that trifluoroacetic acid acts as a source of oxygen for the oxyarylation step, and isotopic labeling studies support the proposal that the mechanistic pathway involves activation of the alkyne by the acidic medium. Various kinds of substituents are tolerated, which should prove valuable for structural and biological investigations.

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More research is needed about 7-Bromo-2-chloroquinoxaline

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The invention relates to new quinoxaline, quinoline and quinazolinone derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

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What I Wish Everyone Knew About 49679-45-0

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(Chemical Equation Presented) Derivatives of the hitherto unknown ring system, pyrazolo[4?,3?:5,6]pyrano[2,3-b]quinoxalin-4(1H)-one, are synthesized in one step from the corresponding 1-substuituted or 1,3-disubstituted 2-pyrazolin-5-ones and 3-chloroquinoxaline-2-carbonyl chloride using calcium hydroxide in boiling 1,4-dioxane. The parent system carrying no substituent in positions 1 and 3 is obtained upon treatment of the 1-PMB (p-methoxybenzyl) protected congener with trifluoroacetic acid. Detailed NMR spectroscopic investigations including unambiguous chemical shift assignments of all 1H, 13C, and 15N resonances of the obtained tetracycles are reported.

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