504423-47-6Relevant academic research and scientific papers
Discovery of derivatives of 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: novel, hypoxia-selective HIF-1α inhibitors with strong antiestrogenic potency
Buravchenko, Galina I.,Bykov, Evgeny E.,Dezhenkova, Lyubov G.,Korlukov, Alexander A.,Monzote Fidalgo, Lianet,Scherbakov, Alexander M.,Shchekotikhin, Andrey E.,Solovieva, Svetlana E.,Sorokin, Danila V.
, (2020)
In this article, we describe the synthesis of 3-phenylquinoxaline-2-carbonitrile 1,4-dioxides bearing cyclic diamine residues at positions 6 or 7; the synthesis is based on the nucleophilic substitution of halogens. All synthesized 6(7)-aminoquinoxaline-2-carbonitrile 1,4-dioxides 3–6 demonstrated higher cytotoxicity and hypoxia selectivity compared to the reference agent tirapazamine against breast adenocarcinoma cell lines (MCF7, MDA-MB-231). The structure and position of the diamine residue considerably affects the antiproliferative properties of the quinoxaline-2-carbonitrile 1,4-dioxides. The introduction of a halogen atom at position 7 in the quinoxaline ring of 4a considerably increases the cytotoxicity of compounds 5a and 6a under both normoxic and hypoxic conditions. However, the most hypoxia-selective derivatives were non-halogenated 7-aminosubstituted 3-phenylquinoxaline-2-carbonitrile 1,4-dioxides 3a–j. Of the 32 novel synthesized derivatives, approximately 20 of the 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides demonstrated high antiproliferative potency against wild type leukemia cells K562 and drug-resistant subline K562/4 with the expression of p-glycoprotein (p-gp) compared to the reference agent doxorubicin, which exhibited one order of magnitude lower activity towards K562/4 cells than towards K562 cells. Lead compounds 5a and 3f inhibited HIF-1α expression and activity and induced apoptosis in hypoxic tumor cells, which was confirmed by poly(ADP-ribose)polymerase (PARP) cleavage. Moreover, 5a and 3f showed strong antiestrogenic potencies in MCF7 breast cancer cells. Thus, the described series of quinoxaline 1,4-dioxides has high anticancer potential and good aqueous solubility. Therefore, these compounds are promising for further drug development of hypoxia-targeted anticancer agents.
METHOD FOR TREATING A TUMOUR DISEASE AND METHOD FOR SELECTIVELY INHIBITING TUMOUR CELL GROWTH USING A QUINOXALINE-1,4-DIOXIDE DERIVATIVE
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Paragraph 0020; 0021, (2017/03/21)
The present invention relates to the fields of pharmacology and medicine, in particular, to the medical application of 6,7-difluoro-3-phenyl-2-cyanoquinoxaline 1,4-dioxide of formula I: for inhibition of tumor cell growth or treatment of tumor diseases.
Synthesis and antimalarial activity of new 3-arylquinoxaline-2-carbonitrile derivatives
Zarranz, Belen,Jaso, Andres,Aldana, Ignacio,Monge, Antonio,Maurel, Severine,Deharo, Eric,Jullian, Valerie,Sauvain, Michel
, p. 754 - 761 (2007/10/03)
New series of 3-arylquinoxaline-carbonitrile derivatives have been synthesized from various 5-substituted or 5,6-disubstituted benzofuroxanes and tested for their in vitro and in vivo activity against the erythrocytic development of Plasmodium falciparum
Fluorine-containing heterocycles: VII. Nucleophilic substitution in 6,7-difluoroquinoxalines
Kotovskaya,Romanova,Charushin,Chupakhin
, p. 1046 - 1052 (2007/10/03)
For the purpose of biological screening, a number of new quinoxalines have been synthesized via fluorine replacement in 2,3-disubstituted 6,7-difluoroquinoxaline 1,4-dioxides and their deoxygenated derivatives by reactions with dialkylamines, sodium azide, and sodium methoxide.
