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Synthesis, SAR study, and biological evaluation of novel 2,3-dihydro-1H-imidazo[1,2-a]benzimidazole derivatives as phosphodiesterase 10A inhibitors

Phosphodiesterase 10A (PDE10A) inhibitors were designed and synthesized based on the dihydro-imidazobenzimidazole scaffold. Compound 5a showed moderate inhibitory activity and good permeability, but unfavorable high P-glycoprotein (P-gp) liability for brain penetration. We performed an optimization study to improve both the P-gp efflux ratio and PDE10A inhibitory activity. As a result, 6d was identified with improved P-gp liability and high PDE10A inhibitory activity. Compound 6d also showed satisfactory brain penetration, suppressed phencyclidine-induced hyperlocomotion and improved MK-801-induced working memory deficit.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N554 | ChemSpider

Discovery of 2-Chloroquinoxaline

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Preparation and Reactions of 2-Alkynyl-3-chloroquinoxalines.

2-Alkynyl-3-chloroquinoxalines are prepared from 2,3-dichloroqionoxaline and alk-1-ynes: use of 2-methylbut-3-yn-2-ol, and the removal of acetone with base, yields 2-chloro-3-ethynylqionoxaline.The chloroalkynes are readily converted into pyrrolo- and thieno<2,3-b>qionoxalines. 2-Chloro-3-phenylethynylquinoxaline with potassium hydroxide gives 2-phenylfurano<2,3-b>quinoxaline but other furano-compounds could not be prepared. 2-Chloro-3-(3-hydroxy-3-methylbut-2-ynyl)quinoxaline with ethanolic sodium ethoxide yields 2H-2,2-dimethyl-3-ethoxypyrano<2,3-b>quinoxaline.When 2-ethynyl- or 2-chloro-3-ethynylqionoxaline is heated with morpholine and sulphur, 2-morpholinothieno<2,3-b>quinoxaline is obtained.The structures of these compounds are established by spectroscopic methods.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N514 | ChemSpider

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Synthesis of 2-(2-nitrophenoxy)quinoxaline and its basic hydrolysis in aqueous solutions of non-reactive counter-ion surfactants with bulky head groups

The synthesis of the novel compound 2-(2-nitrophenoxy)quinoxaline (2) is described and its basic hydrolysis was studied in the presence of non-reactive counter-ion surfactants with different head group size. Micellar effects upon the reaction of OH- with (2) were analyzed by using a mass-action-like equation.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N565 | ChemSpider

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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 1448-87-9 is helpful to your research. Application of 1448-87-9

Application of 1448-87-9, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 1448-87-9, molcular formula is C8H5ClN2, introducing its new discovery.

Quinoxalinyloxy ethers as selective weed control agents

This invention relates to herbicidal quinoxalinyloxy ethers, herbicidal compositions containing said ethers, and methods of using said compounds as herbicides.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N461 | ChemSpider

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DIAZASPIRODECANE OREXIN RECEPTOR ANTAGONISTS

The present invention is directed to diazaspirodecane compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N483 | ChemSpider

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Synthesis of PJOV56, a new quinoxalinyl-hydrazone derivative able to induce autophagy and apoptosis in colorectal cancer cells, and related compounds

Quinoxaline derivatives are reported as antineoplastic agents against a variety of human cancer cell lines, with some compounds being submitted to clinical trials. In this work, we report the synthesis, characterization and cytotoxicity potential of a new series of quinoxalinyl-hydrazones. The most cytotoxic compound was (E)-2-[2-(2-pyridin-2-ylmethylene)hydrazinyl]quinoxaline (PJOV56) that presented a time-dependent effect against HCT-116 cells. After 48 h of incubation, PJOV56 was able to induce autophagy and apoptosis of HCT-116 cells, mediated by upregulation of Beclin 1, upregulation of LC3A/B II and activation of caspase 7. Apoptosis was induced along with G0/G1 cell cycle arrest at the highest concentration of PJOV56 (6.0 muM). Thus, PJOV56 showed a dose-dependent mode of action related to induction of autophagy and apoptosis in HCT-116 cells.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N523 | ChemSpider

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Phosphine-functionalized NHC Ni(II) and Ni(0) complexes: Synthesis, characterization and catalytic properties

Two families of nickel complexes bearing chelating diphenylphosphine-functionalized NHC ligands [NiII(ArNHCPPh2)(allyl)]Cl 1a (Ar = Mes); 1b, (Ar = 2,6-iPr2-C6H3) and [Ni0(ArNHCPPh2)(alkene)] 2a (Ar = 2,6-iPr2-C6H3, alkene = styrene); 2b (Ar = 2,6-iPr2-C6H3, alkene = diethyl fumarate) have been prepared and fully characterized. VT-NMR experiments in solution reveal that the allyl derivatives 1a-b are stereochemically nonrigid. The solid-state structure of the Ni0 derivative 2b is also reported. These complexes display interesting catalytic properties in various cross-coupling reactions. The precatalyst [Ni0(ArNHCPPh2)(styrene)] 2a was found to be the most active system. The bulkiness of the N-substituent on the imidazole ring and the low oxidation state of the metal center in 2a accounted for its enhanced catalytic performance. This system catalyzed effectively the coupling of (hetero)aryl chlorides with a range of nucleophiles including Grignard reagents, boronic acids, secondary amines and indoles.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N674 | ChemSpider

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Discovery of Orally Bioavailable and Liver-Targeted Hypoxia-Inducible Factor Prolyl Hydroxylase (HIF-PHD) Inhibitors for the Treatment of Anemia

We report herein the design and synthesis of a series of orally active, liver-targeted hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitors for the treatment of anemia. In order to mitigate the concerns for potential systemic side effects, we pursued liver-targeted HIF-PHD inhibitors relying on uptake via organic anion transporting polypeptides (OATPs). Starting from a systemic HIF-PHD inhibitor (1), medicinal chemistry efforts directed toward reducing permeability and, at the same time, maintaining oral absorption led to the synthesis of an array of structurally diverse hydroxypyridone analogues. Compound 28a was chosen for further profiling, because of its excellent in vitro profile and liver selectivity. This compound significantly increased hemoglobin levels in rats, following chronic QD oral administration, and displayed selectivity over systemic effects.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N615 | ChemSpider

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Tyrosine kinase inhibitors. 5. Synthesis and structure-activity relationships for 4-[(phenylmethyl)amino]- and 4-(phenylamino)quinazolines as potent adenosine 5′-triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth factor receptor

A series of 4-substituted quinazolines and related compounds have been prepared and evaluated for their ability to inhibit the tyrosine kinase activity of the epidermal growth factor receptor on a phospholipase C-gamma1- derived substrate. The results show a narrow structure-activity relationship (SAR) for the basic ring system, with quinazoline being the preferred chromophore and benzylamino and anilino the preferred side chains. In the 4- anilino series, substitution on the 3-position of the phenyl ring with small lipophilic electron-withdrawing groups provided analogues with enhanced potency. Two series of compounds [4-(phenylmethyl)amino and 4-(3- bromophenyl)amino] were studied to determine SARs for quinazoline substituents. In the more active 4-(3-bromophenyl)amino series, electron- donating groups (NH2, OMe) at the 6- or 7-position increased activity, in a pattern consistent with a requirement for high electron density in the vicinity of the 8-position of the quinazoline ring. The 6,7-dimethoxy derivatives were the most effective in both series, with the 4-(3- bromophenyl)amino derivative (3) having an IC50 of 0.029 nM, making it by far the most potent reported inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor enzyme.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N669 | ChemSpider

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Modeling Pyran Formation in the Molybdenum Cofactor: Protonation of Quinoxalyl-Dithiolene Promoting Pyran Cyclization

Mononuclear Mo and W enzymes require a unique ligand known as molybdopterin (MPT). This ligand binds the metal through a dithiolene chelate, and the dithiolene bridges a reduced pyranopterin group. Pyran scission and formation have been proposed as a reaction of the MPT ligand that may occur within the enzymes to adjust reactivity at the Mo atom. We address this issue by investigating oxo-Mo(IV) model complexes containing dithiolenes substituted by pterin or quinoxaline and a hydroxyalkyl poised to form a pyran ring. While the pterin-dithiolene model complex exhibits a low energy, reversible pyran cyclization, here we report that pyran cyclization does not spontaneously occur in the quinoxalyl-dithiolene model. However, protonating the quinoxalyl-dithiolene model induces pyran cyclization forming an unstable, pyrano-quinoxalyl-dithiolene complex which subsequently dehydrates and rearranges to a pyrrolo-quinoxlyl-dithiolene complex that was previously characterized. The protonated pyrano-quinoxalyl-dithiolene complex was characterized by absorption spectroscopy and cyclic voltammetry, and these results suggest pyran cyclization leads to a significant change in the Mo electronic structure exhibited as a strong intraligand charge transfer (ILCT) transition and 370 mV positive shift of the Mo(V/IV) reduction potential. The influence of protonation on quinoxaline reactivity supports the hypothesis that the local protein environment in the second coordination sphere of molybdenum cofactor (Moco) could control pyran cyclization. The results also demonstrate that the remarkable chemical reactivity of the pterin-dithiolene ligand is subtly distinct and not reproduced by the simpler quinoxaline analog that is often used to replace pterin in synthetic Moco models.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N590 | ChemSpider