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A series of new 1,4-dihydro-1,2,4-triazolo[4,3-a]quinoxaline-1,4-diones has been reported. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated rat passive cutaneous anaphylaxis (PCA). Most of this new class of antiallergic agents showed good activity in the RMC and PCA tests. The most potent compound, 2-acetyl-7-chloro-5-n-propyl-1,2,4-triazolo[4,3-a]quinoxaline-1,4-dione, with an I50 value of 0.1 muM, is 30 times more potent than disodium cromoglycate (DSCG) in the RMC assay.

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A series of 4-hydroxy-3-nitroquinolin-2(1H)-ones (HNQs) was synthesized by nitration of the corresponding 2,4-quinolinediols. The HNQs were evaluated as antagonists at the glycine site of NMDA receptors by inhibition of [3H]DCKA binding to rat brain membranes. Selected HNQs were also tested for functional antagonism by electrophysiological assays in Xenopus oocytes expressing either 1a/2C subunits of NMDA receptors or rat brain AMPA receptors. The structure-activity relationships (SAR) of HNQs showed that substitutions in the 5-, 6-, and 7-positions in general increase potency while substitutions in the 8-position cause a sharp reduction in potency. Among the HNQs tested, 5,6,7-trichloro HNQ (8i) was the most potent antagonist with an IC50 of 220 nM in [3H]DCKA binding assay and a K(b) of 79 nM from electrophysiological assays. Measured under steady-state conditions HNQ 8i is 240-fold selective for NMDA over AMPA receptors. The SAR of HNQs was compared with those of 1,4-dihydroquinoxaline-2,3-diones (QXs) and 1,2,3,4-tetrahydroquinoline-2,3,4-trione 3-oximes (QTOs). In general, HNQs have similar potencies to QXs with the same benzene ring substitution pattern but are about 10 times less active than the corresponding QTOs. HNQs are more selective for NMDA receptors than the corresponding QXs and QTOs. The similarity of the SAR of HNQs, QXs, and QTOs suggested that these three classes of antagonists might bind to the glycine site in a similar manner. With appropriate substitutions, HNQs represent a new class of potent and highly selective NMDA receptor glycine site antagonists.

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Reference:
Quinoxaline – Wikipedia,
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A series of new 1,4-dihydro-1,2,4-triazolo[4,3-a]quinoxaline-1,4-diones has been reported. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated rat passive cutaneous anaphylaxis (PCA). Most of this new class of antiallergic agents showed good activity in the RMC and PCA tests. The most potent compound, 2-acetyl-7-chloro-5-n-propyl-1,2,4-triazolo[4,3-a]quinoxaline-1,4-dione, with an I50 value of 0.1 muM, is 30 times more potent than disodium cromoglycate (DSCG) in the RMC assay.

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A series of 4-hydroxy-3-nitroquinolin-2(1H)-ones (HNQs) was synthesized by nitration of the corresponding 2,4-quinolinediols. The HNQs were evaluated as antagonists at the glycine site of NMDA receptors by inhibition of [3H]DCKA binding to rat brain membranes. Selected HNQs were also tested for functional antagonism by electrophysiological assays in Xenopus oocytes expressing either 1a/2C subunits of NMDA receptors or rat brain AMPA receptors. The structure-activity relationships (SAR) of HNQs showed that substitutions in the 5-, 6-, and 7-positions in general increase potency while substitutions in the 8-position cause a sharp reduction in potency. Among the HNQs tested, 5,6,7-trichloro HNQ (8i) was the most potent antagonist with an IC50 of 220 nM in [3H]DCKA binding assay and a K(b) of 79 nM from electrophysiological assays. Measured under steady-state conditions HNQ 8i is 240-fold selective for NMDA over AMPA receptors. The SAR of HNQs was compared with those of 1,4-dihydroquinoxaline-2,3-diones (QXs) and 1,2,3,4-tetrahydroquinoline-2,3,4-trione 3-oximes (QTOs). In general, HNQs have similar potencies to QXs with the same benzene ring substitution pattern but are about 10 times less active than the corresponding QTOs. HNQs are more selective for NMDA receptors than the corresponding QXs and QTOs. The similarity of the SAR of HNQs, QXs, and QTOs suggested that these three classes of antagonists might bind to the glycine site in a similar manner. With appropriate substitutions, HNQs represent a new class of potent and highly selective NMDA receptor glycine site antagonists.

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Reference:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N298 | ChemSpider

 

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Novel 2 and 3-substituted quinoxaline derivatives were synthesized through various synthetic pathways, among which cyanoacetamide and cyanoacetohydrazide quinoxaline derivatives 4a-c and 11a-c, respectively, were synthesized. Furthermore, methoxy quinoxaline derivatives 3c and quinoxaline derivatives bearing substituted pyridines 6a,b, 12a,b, and 13a,b were designed to be synthesized. However, we have synthesized acrylohydrazide 5a,b and 7/acrylamide derivatives, Schiff base analogues 14a-f, pyrazole derivatives 15a-e, amide derivatives 16a-f, guanidine derivatives 16 g,h as well as, quinoxalin-2-methylallyl propionate derivative 14g. All the synthesized compounds were confirmed via spectral data and elemental analyses. Moreover, the newly synthesized compounds were evaluated for their antimicrobial activity (Gm +ve, Gm ?ve in comparison to Gentamycin a standard) and fungi (in comparison to Ketoconazole as a standard). Thus, compound 16b showed promising antimicrobial activity against B. subtilis, P. vulgaris, and S. mutants with values ranging from 20 to 27-mm zone of inhibition. While compounds 5a, 14e,f, and 16a,c,d,g,h showed potent antimicrobial activity. Moreover, the National Cancer Institute (NCI) selected 20 compounds that were submitted for anticancer screening against 60 types of cancer cell lines. The most active compounds are 5b and 12a where compound 5b containing 2,4-dichlorophenyl moiety at cyanoacetamide linkage of hydrazine quinoxaline backbone exerted significant growth inhibition activity against Leukemia MOLT-4, Renal cancer UO-31, and Breast cancer MCF-7. In addition, compound 12a having 4,6-diaminopyridinone side chain at position-3 of quinoxaline nucleus exhibited remarkable anticancer activity against renal cancer UO-31.

Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. COA of Formula: C8H6N2O2, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 15804-19-0, in my other articles.

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The oxidation reaction of a series of quinoxaline derivatives, using KMnO4 in the presence or absence of NaOH, are described.Neutral oxidation of 2-chloro- and 2,3-dichlorodioxalines 2-4 afforded the corresponding chloro- and dichloropyrazinedicarboxilic acids 13 and 14 in good yield.On the other hand, oxidation of quinoxalin-2(1H)-one and 1,4-dihydroquinoxaline-2,3-dione derivatives in alkaline medium gave different products, with the quinoxalin-2(1H)-one (5) forming 1,4-dihydroquinoxaline-2,3-dione (9), while various substituted quinoxalin-2,3-dione derivatives (see 9-11) gave a new type of dimeric products.The structural assignments for the new compounds were based on spectroscopic data.

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The first coordination compound of 1,4-dihydro-2,3-quinoxalinedione in ketoamine tautomeric form (denoted as H2qdione) was reported. H 2qdione was obtained by a solid-state reaction of o-phenylenediamine and oxalic acid. Reaction of this ligand with CdCl2 solvothermally yielded a coordination polymer [Cd(H2qdione)Cl2] n, which was structurally characterized by X-ray diffraction and IR spectroscopy. Continuous Cd2Cl2 diamonds form a double-sided comb with terminal H2qdione-kappa2O,O’ as the comb teeth. Interaction of these combs through very extensive pi-pi stacking, C-HA…Cl, and N-HA…Cl hydrogen bonds leads to a novel 3D architecture and significant enhancement of solid-state luminescence of about 10 times compared to the free H2qdione ligand.

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The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via the 5-endo-trig process contrary to Baldwin’s rule. On the other hand, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via the 6-exo-trig process in compliance with Baldwin’s rule. The mechanistic insights of these cyclocondensation reactions using the hard-soft acid-base principle, quantum chemical calculations (density functional theory), and orbital interaction studies rationalize the selectivity switch of benzothiazole-2-carboxylates versus benzazine-3-ones/ benzazine-2,3-diones. The presence of water facilitates these cyclocondensation reactions by lowering of the energy barrier.

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The reaction of 1,4-dihydro-2,3-quinoxalinedione (H2L?) with CuCl2 in the presence of LiOH in DMF has led to the 3D coordination polymer [Cu3L2Cl2(DMF)4]n (1) with an (82 · 10)-a, lig (LiGe), topology, where L2- is 2,3-dioxyquinoxalinate(-2). This compound is the first coordination polymer of any transition metal featuring L2- and contains the ligand in a novel 3.1111 (Harris notation) coordination mode. IR data are discussed in terms of the chemical composition of the polymer and the coordination mode of L2-. Variable-temperature (2-300 K) magnetic susceptibility and variable-field (0-5 T) magnetization studies reveal that L2- propagates weak antiferromagnetic exchange interactions through its “quinoxaline” moiety.

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Ytterbium triflate are found to catalyze efficiently the Phillips-type heterocyclization reactions of 1,2-phenylenediamine and alkyl oxalate under solvent-free and mild conditions to afford the corresponding quinoxaline-2,3-dione derivatives in high yields. The catalyst could be recovered almost quantitatively from the aqueous layer after the reaction was completed and it could be reused in subsequent reaction without decrease in activity.

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