22047-25-2Relevant articles and documents
Novel thiosemicarbazones derived from formyl- and acyldiazines: Synthesis, effects on cell proliferation, and synergism with antiviral agents
Easmon,Heinisch,Holzer,Rosenwirth
, p. 3288 - 3296 (1992)
The synthesis of a series of novel thiosemicarbazones (TSC's) derived from various alkyl diazinyl (3-pyridazinyl, 4-pyrimidinyl, 2-pyrazinyl) ketones and 3-pyridazinecarbaldehyde and their evaluation against herpes simplex virus (HSV) and human immunodeficiency virus (HIV) as well as the determination of their cytotoxicity are described. In addition, the effects of combination of such TSC's with the well-known antiviral drugs acyclovir (ACV) and 3'-azido-3'-deoxythymidine (AZT) were studied. Under our experimental conditions, i.e. determination of virus-induced cytopathic effect upon infection of HUT78 cells with HSV-1 and upon infection of MT4 cells with HIV-1, no antiviral activity could be detected with any of the TSC's. However, pronounced effects on proliferation of these rapidly growing T4 lymphocyte cell lines were observed. Clear structure-activity relationships with regard to these cytotoxic effects could be established: compared to pyridine, pyrazine, or pyrimidine-derived TSC's most of the 3- pyridazinyl congeners investigated are less cytotoxic: introduction of a methyl group into C-6 of the pyridazine system or prolongation of the acyl moiety in these compounds has essentially no influence; all compounds bearing an N,N-dimethylamino or a cycloamino substituent are much more toxic than those with an NH2 or NHR substituent; the nature of R in the latter type of compounds has only moderate influence. It has been reported that combination of TSC's with the antiviral agent acyclovir (ACV) results in potentiation of this well-known drug. We evaluated the potential of our series of novel TSC's in combination with ACV for inhibition of HSV-1-induced cytopathic effect in HUT78 cells and in combination with 3'-azido-3'-deoxythymidine (AZT) for inhibition of HIV-1-induced cytopathic effect in MT4 cells. Only four compounds out of this series, all characterized by an unsubstituted NH2 group, exhibited moderate synergism with the above mentioned antiviral drugs. Our results do not support the previously expressed opinion that TSC's are selective antiviral agents. In our test systems no evidence for inhibition of virus-induced cytopathic effect was obtained. The TSC derivatives exhibited a broad range of cytotoxic effects, some at concentrations considerably below those reported to have antiviral efficacy. Several of our novel diazine- derived compounds proved advantageous over the previously described pyridine analogues with regard to cytotoxicity. Moderate synergism could be detected for relatively noncytotoxic TSC's with the antiviral drugs ACV (antiherpes) and AZT (anti-HIV).
Highly chemoselective deoxygenation of N-heterocyclic: N -oxides under transition metal-free conditions
Kim, Se Hyun,An, Ju Hyeon,Lee, Jun Hee
supporting information, p. 3735 - 3742 (2021/05/04)
Because their site-selective C-H functionalizations are now considered one of the most useful tools for synthesizing various N-heterocyclic compounds, the highly chemoselective deoxygenation of densely functionalized N-heterocyclic N-oxides has received much attention from the synthetic chemistry community. Here, we provide a protocol for the highly chemoselective deoxygenation of various functionalized N-oxides under visible light-mediated photoredox conditions with Na2-eosin Y as an organophotocatalyst. Mechanistic studies imply that the excited state of the organophotocatalyst is reductively quenched by Hantzsch esters. This operationally simple technique tolerates a wide range of functional groups and allows high-yield, multigram-scale deoxygenation. This journal is
Method for synthesizing 2-acetyl pyrazine
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Paragraph 0022-0029, (2019/06/27)
The invention relates to the field of chemical organic synthesis, in particular to a method for synthesizing 2-acetyl pyrazine. The method comprises the following steps: (1) preparation of a Grignardreagent: adding metallic magnesium, an anhydrous polar solvent, elemental iodine and methyl chloride into a pressure vessel, and stirring to prepare the Grignard reagent; (2) adding reaction: adding 2-cyanopyrazine, tetrahydrofuran, a catalyst and the Grignard reagent into a reactor, and refluxing and condensing to obtain an intermediate product; (3) hydrolyzing: adding water into the intermediateproduct, adjusting the pH value by using dilute acid, stirring and refluxing, and then adjusting to be neutral; and finally, extracting with toluene; and (4) aftertreatment: desolventizing a tolueneextracting solution, dissolving desolventized solid with ethanol, adding activated carbon, filtering, and cooling to obtain a white solid P1; and recrystallizing with the ethanol to obtain the 2-acetylpyrazine. According to the method, a monovalent copper salt is adopted as a catalyst, the yield of 2-acetylpyrazine is increased to be 69%, meanwhile, the reaction speed is increased, and the synthesis reaction temperature is also reduced.
