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Novel Octahydropyrrolo[3,4- c ]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate

The preclinical characterization of novel octahydropyrrolo[3,4-c]pyrroles that are potent and selective orexin-2 antagonists is described. Optimization of physicochemical and DMPK properties led to the discovery of compounds with tissue distribution and duration of action suitable for evaluation in the treatment of primary insomnia. These selective orexin-2 antagonists are proven to promote sleep in rats, and this work ultimately led to the identification of a compound that progressed into human clinical trials for the treatment of primary insomnia. The synthesis, SAR, and optimization of the pharmacokinetic properties of this series of compounds as well as the identification of the clinical candidate, JNJ-42847922 (34), are described herein.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N611 | ChemSpider

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Synthesis and Minisci reactions of organotrifluoroborato building blocks

Copper-catalyzed borylation of a variety of organic halides with bis(pinacolato)diboron allows the preparation of diverse potassium organotrifluoroborates. The reactions are mild and general, providing access to a variety of interesting, boron-containing building blocks, including those containing piperidine, pyrrole, azetidine, tetrahydropyran, and oxetane substructures. Representative Minisci reactions are reported for select examples.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N664 | ChemSpider

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Application of 1448-87-9, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.1448-87-9, Name is 2-Chloroquinoxaline, molecular formula is C8H5ClN2. In a article£¬once mentioned of 1448-87-9

Tuning photophysical and electrochemical properties of heteroleptic cationic iridium(III) complexes containing substituted 2-phenylquinoxaline and biimidazole

Design and syntheses of four red phosphorescent heteroleptic cationic iridium(III) complexes containing two substituted phenylquinoxaline (pqx) or benzo[b]thiophen-2-yl-pyridin (btp) main ligands and one 2,2?-biimidazole (H2biim) ancillary ligand are reported: [(pqx)2Ir(biim)]Cl (1), [(dmpqx)2Ir(biim)]Cl (2), [(dfpqx)2Ir(biim)]Cl (3), [(btp)2Ir(biim)]Cl (4). Complex 1 showed a distorted octahedral geometry around the iridium(III) metal ion with cis metallated carbons and trans nitrogen atoms. The absorption, emission and electrochemical properties were systematically evaluated. The complexes exhibited red phosphorescence in the spectral range of 580 to 620 nm with high quantum efficiencies of 0.58 – 0.78 in both solution and solid-state at room temperature depending on the cyclometalated main ligands. The cyclic voltammetry of the complexes (1-3) showed a metal-centered irreversible oxidation in the range of 1.40 to 1.90 V as well as two quasi reversible reduction waves from -1.15 to -1.45 V attributed to the sequential addition of two electrons to the more electron accepting heterocyclic portion of two distinctive cyclometalated main ligands, whereas complex 4 showed a reversible oxidation potential at 1.24 V and irreversible reduction waves at -1.80 V.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N683 | ChemSpider

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Inexpensive Radical Methylation and Related Alkylations of Heteroarenes

A simple method for the introduction of a methyl and higher aliphatic group to various heteroarenes using very inexpensive reagents is described. It is based on the radical addition of a carboxylic xanthate followed by decarboxylation. Depending on the heteroarene structure, the decarboxylation can be spontaneous or induced by heating in N,N-dimethylacetamide or N-methyl pyrrolidone in a microwave oven.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N599 | ChemSpider

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 1448-87-9, name is 2-Chloroquinoxaline, introducing its new discovery. SDS of cas: 1448-87-9

Visible Light-Mediated Direct Decarboxylative C-H Functionalization of Heteroarenes

The direct visible light-mediated C-H alkylation of heteroarenes using aliphatic carboxylic acids is reported. This mild method proceeds at low catalyst loadings (0.5 mol %) and has a high functional group tolerance and a broad substrate scope. Notably, functionalization of (iso)quinoline, pyridine, phthalazine, benzothiazole, and other heterocyclic derivatives with both cyclic and acyclic primary, secondary, and tertiary carboxylic acids as well as amino and fatty acids proceeded under the standard conditions at room temperature. This protocol enables the rapid conversion of abundant feedstock materials into medically relevant “drug-like” moieties.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N589 | ChemSpider

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Ligand-Accelerated Iron Photocatalysis Enabling Decarboxylative Alkylation of Heteroarenes

A mild, practical protocol for the decarboxylative alkylation of heteroarenes has been accomplished via iron photocatalysis. A diverse range of carboxylic acids readily undergo oxidative decarboxylation and then couple with a broad array of heteroarenes in this transformation. The photoexcited state lifetimes of iron complexes are typically much shorter than those of iridium and ruthenium complexes. Here we describe our effort on iron photocatalysis by utilizing the intramolecular charge transfer pathway of iron-carboxylate complexes.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N612 | ChemSpider

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DIPEPTIDYL PEPTIDASE IV INHIBITOR

A compound represented by general formula (I):A-B-D or a pharmacologically acceptable salt thereof.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N480 | ChemSpider

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Autoxidative C(sp2)-P Formation: Direct Phosphorylation of Heteroarenes under Oxygen, Metal-Free, and Solvent-Free Conditions

We reveal here a direct autoxidative phosphorylation of heteroarenes induced by oxygen under metal-free and solvent-free conditions. This new methodology provides an economical, operationally simple, and environmentally friendly approach toward (Het)C(sp2)-P formation with medium to excellent yields. Heteroarenes including thiazole and quinoxaline derivatives are applicable under standard conditions, which is testified via a radical mechanism.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N617 | ChemSpider

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Electric Literature 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.

Copper catalysed alkylation of heteroaryl chloride via migratory insertion of carbenes

Cross-coupling reaction involving Cu catalysed carbene migratory insertion with N-tosylhydrazones as the reaction partner with various substituted cyanuric chloride were studied, which has been recognized as a new type of cross-coupling reaction. Cu-carbene migratory insertion is proposed to play the key role in this transformation to form C-C bond from heterohalides with various tosylhydrazones. Salient features of this reactions are (i) no stoichiometric organometallic reagents are required (ii) less toxic and step economical reaction (iii) easy to handle, to get moderate to excellent yields. Outcome of this reaction produces 1,1-heterodiaryl alkanes.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N641 | ChemSpider

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Addressing phototoxicity observed in a novel series of biaryl derivatives: Discovery of potent, selective and orally active phosphodiesterase 10A inhibitor ASP9436

Abstract We synthesized several biaryl derivatives as PDE10A inhibitors to prevent phototoxicity of 2-[4-({[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline (1) and found that the energy difference between the energy-minimized conformation and the coplanar conformation of the biaryl moiety helped facilitate prediction of the phototoxic potential of biaryl compounds. Replacement of the quinoline ring of 1 with N-methyl benzimidazole increased this energy difference and prevented phototoxicity in the 3T3 NRU test. Further optimization identified 1-methyl-5-(1-methyl-3-{[4-(1-methyl-1H-benzimidazol-4-yl)phenoxy]methyl}-1H-pyrazol-4-yl)pyridin-2(1H)-one (38b). Compound 38b exhibited good selectivity against other PDEs, and oral administration of 38b improved visual-recognition memory deficit in mice at doses of 0.001 and 0.003 mg/kg in the novel object recognition test. ASP9436 (sesquiphosphate of 38b) may therefore be used for the treatment of schizophrenia with a low risk of phototoxicity.

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N592 | ChemSpider