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Design, synthesis and biological evaluation of (E)-2-(2-arylhydrazinyl) quinoxalines, a promising and potent new class of anticancer agents

A series of forty-seven quinoxaline derivatives, 2-(XYZC6H 2CHN-NH)-quinoxalines, 1, have been synthesized and evaluated for their activity against four cancer cell lines: potent cytotoxicities were found (IC50 ranging from 0.316 to 15.749 muM). The structure-activity relationship (SAR) analysis indicated that the number, the positions and the type of substituents attached to the aromatic ring are critical for biological activity. The activities do not depend on the electronic effects of the substituents nor on the lypophilicities of the molecules. A common feature of active compounds is an ortho-hydroxy group in the phenyl ring. A potential role of these ortho-hydroxy derivatives is as N,N,O-tridentate ligands complexing with a vital metal, such as iron, and thereby preventing proliferation of cells. The most active compound was (1: X,Y = 2,3-(OH)2, Z = H), which displayed a potent cytotoxicity comparable to that of the reference drug doxorubicin.

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TAUTOMERISM OF DERIVATIVES OF AZINES. 17. EFFECT OF SOLVENTS ON THE POSITION OF THE AZINYL-YLIDENE TAUTOMERIC EQUILIBRIUM OF SUBSTITUTED AZINYLMETHANES

The effect of solvents on the position of the azinyl-ylidene tautomeric equilibrium in series of azinylmethanes was studied.It was shown that an increase in the polarity of the solvent leads to stabilization of the ylidene tautomer; the sensitivity of the tautomeric equilibrium to the effects of the solvent depends on the form of the side fragment that undergoes tautomerization.It was concluded that stabilization of the ylidene tautomeric form by polar solvents is a general tendency in series of prototropic equilibrium of the azinyl-ylidene type as a whole.

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Parallel synthesis of N-arylpiperazines using polymer-assisted reactions

A series of N-arylpiperazines were prepared in a parallel fashion using palladium-catalyzed cross-coupling, or nucleophilic aromatic displacement chemistries, and polymer-assisted sequestration and purification techniques as key steps.

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Phenyl-piperazine methanone derivatives, substituted by heterocyclic groups

The present invention relates to compounds of the general formula I [image] wherein R1 is the group [image] and R2, R?, R?, R3, R4, R5, R6, R7, X1, X1?, X2, and N are as defined in the specification. Compounds of the invention are useful for the treatment of neurological and neuropsychiatric disorders.

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FUSED HETEROCYCLIC COMPOUNDS AS OREXIN RECEPTOR MODULATORS

Certain disubstituted 3,8-diaza-bicyclo[4.2.0]octane and 3,6-diazabicyclo [3.2.0]heptane are described, which are useful as orexin inhibitors. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.

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A fragrant nitrile or heteroaromatic nitrile compound preparation method (by machine translation)

The invention discloses a fragrant nitrile or heteroaromatic nitrile compound preparation method, the method comprises the following steps: under protection of inert gas, in a solvent, in the nickel catalyst and ligand, metal zinc, and under the action of the additive, the cyano reagent with a halo aromatic hydrocarbon or the halogenating is mixed aromatic hydrocarbon reaction can be. The present invention provides a preparation method, the use of a readily available and inexpensive nickel catalyst and ligand, can be mild, efficiently realize the halogenating is mixed halo aromatic hydrocarbon or aromatic hydrocarbon can particularly will be cheap and easily obtained but the reaction low activity of the chlorinated aromatic hydrocarbon or aromatic hydrocarbon […] with toxicity is relatively small of the cyano reagent reaction, to prepare the fragrant nitrile or heteroaromatic nitrile compounds. Preparation method of this invention not only has simple operation, moderate, high efficiency and the like, but also has good functional group compatibility and universality and other characteristics of the substrate. (by machine translation)

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Surgical Cleavage of Unstrained C(sp3)?C(sp3) Bonds in General Alcohols for Heteroaryl C?H Alkylation and Acylation

We reported herein a predictable and surgical cleavage of carbon-carbon bond in alcohols. A wide range of 1, 2 and 3 alcohols including sugars and steroids without ring strain or steric hindrance were all compatible with this system. Also it offered a green and practical strategy for generation of alkyl/acyl radicals using alcohols as the sources. Besides, the features of visible-light-initiation, catalyst and metal free, excellent selectivity and mild conditions make it valuable and attractive. (Figure presented.).

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Anti-quorum and DNA cleaving agent

The anti-quorum and DNA cleaving agent is directed to a ruthenium complex formulated from dichloro-(eta6-p-cymene) ruthenium(II) dimer and 2-chloroquinoxaline, the complex having the formula: The reaction cleaves the dimer, leaving a half-sandwich ruthenium complex with an eta6 coordination bond to the arene ligand and an Ru?N bond attaching the chloroquinoxaline to the ruthenium complex. The agent has an anti-quorum sensing effect on bacteria, inhibiting the formation of biofilm and inhibiting bacterial virulence. The agent also binds to DNA and may cleave the DNA, e.g., at the N7 base pair of guanine, due to a hydrolytic mechanism, suggesting potential use as an anticancer or antitumor agent.

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Discovery of pyrrolo[2,1-f][1,2,4]triazine C6-ketones as potent, orally active p38alpha MAP kinase inhibitors

Pyrrolo[2,1-f][1,2,4]triazine based inhibitors of p38alpha have been prepared exploring functional group modifications at the C6 position. Incorporation of aryl and heteroaryl ketones at this position led to potent inhibitors with efficacy in in vivo models of acute and chronic inflammation.

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Synthesis of new arylaminoquinoxalines and their antimalarial activity in mice

2-Arylaminoquinoxalines were prepared by the condensation of 2-chloroquinoxaline with the appropriate Mannich bases in the presence of HCI. To synthesize the Mannich bases, 4-acetamidophenol was reacted with formaldehyde and dialkylamine to yield 3-[(dialkylamino) methyl]-4-hydroxyacetanilide, followed by hydrolysis. Antimalarial activities of the new arylaminoquinoxalines were evaluated against the rodent malaria parasite Plasmodium yoelii at a dose of 75 mg kg-1. Three compounds synthesized (2-[3-[(diethylamino) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2b), 2-[3-[(pyrrolidinyl) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2f), and 2-[3-[(piperidinyl) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2g)) showed moderate antimalarial activity.

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