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Design and synthesis of new quinoxaline derivatives as anticancer agents and apoptotic inducers

The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds VIId, VIIIa, VIIIc, VIIIe and XVa exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound VIIIc induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound VIIIc could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line.

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BICYCLIC DERIVATIVES AS CETP INHIBITORS

The present invention relates to novel compounds of formula (I): or a pharmaceutical composition thereof, with all the variables being defined in the text. The present invention further relates to the use of the compounds herein for treatment of or delay progression to overt to diseases in which CETP is involved.

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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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Facile synthesis of 6-trichloromethylpterin and 2-chloro-3- trichloromethylquinoxaline along with a library of trichloromethyl heterocycles using N-chlorosuccinimide and triphenyl phosphine

A general synthesis of 6-trichloromethylpterin, 2-chloro-3- trichloromethylquinoxaline and 2-amino-7-trichloromethyl-1,8-naphthyridine along with a series of trichloromethyl heterocycles (1-11) has been reported in one-pot mild neutral condition in good yield. This method is compared with the usual method using phosphorus pentachloride in phosphorus oxychloride. Copyright

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REACTION OF QUINOXALINES WITH beta,gamma-UNSATURATED GRIGNARD REAGENTS. SYNTHESIS OF ALLYL-, ALLENYL-, PROPARGYL-QUINOXALINE DERIVATIVES.

Mono- and bis-addition reactions of the beta,gamma-unsaturated Grignard reagents 2 and 6 to the C=N bonds of quinoxalines 1 afford high yields of dihydroquinoxalines 4 and tetrahydroquinoxalines 3.Dehydrogenation of 4g-l and 3a-c with DDQ leads to allylic quinoxalines 1i-m and 1e-g respectively in very good yields.Allylic and propargylic quinoxalines 1m and 1s can conveniently be synthesized by “cross-coupling” of 2-chloro-3-methylquinoxaline with 2c and 6a.

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Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress

We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40?Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4.

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ORGANOMETALLIC IRIDIUM COMPLEX, LIGHT-EMITTING ELEMENT, LIGHT-EMITTING DEVICE, AND LIGHTING DEVICE

An organometallic iridium complex that has high emission efficiency and a long lifetime and emits deep red light (emission wavelength: around 700 nm) is provided. The organometallic iridium complex has a ligand that is represented by General Formula (G0) and has at least a dimethyl phenyl group and a quinoxaline skeleton. In the formula, R1 to R3 separately represent an alkyl group having 1 to 6 carbon atoms, a phenyl group, or a phenyl group having an alkyl group having 1 to 6 carbon atoms as a substituent.

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Synthesis of novel tricyclic heterocycles from 2[3-methyl -1,2- dihydroquinoxalin – 2 – Ylidene] malononitrile

A NUMBER of pyrrolo[1,2-a]quinoxalines (3a-f), pyrimido[l,6ajquino-xalines (5a-c, 10. 13). pyrido[l,2-a]quinoxalines (6. 7a.b. 8a.b. 14). [1.3]thiazino-[3,4-a]quinoxa[ines (9. 11) and [l.3]oxazino[3,4-a]quinoxalines (12a.b) were obtained via interaction of 2-[3-methyl-l.2-dihydrquinoxalin-2- ylidene]malono-nitrile 2 with different reagents.

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Facile and efficient regioselective synthesis of 1-(3?-substituted quinoxalin-2?-yl)-3-aryl/heteroaryl-5-methylpyrazoles

This report describes an efficient and practical approach for regioselective synthesis of 1-(3?-substituted quinoxalin-2?-yl)-3- aryl/heteroaryl-5-methylpyrazoles (3a-j). Reaction of 2-chloro-3-substituted quinoxalines (1) with 3(5)-methyl-5(3)-aryl-1H-pyrazoles (2) in the presence of sodium hydride furnished the title compounds in excellent yields with good levels of regioselectivity. The present protocol is superior to the existing method, which yielded a mixture of regioisomeric pyrazoles (I, II) and triazolo[4,3-a]quinoxalines (III). Supplemental materials are available for this article. Go to the publisher’s online edition of Synthetic Communications to view the free supplemental file.

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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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