216254-45-4Relevant academic research and scientific papers
Radical Chemistry and Cytotoxicity of Bioreductive 3-Substituted Quinoxaline Di-N-Oxides
Anderson, Robert F.,Yadav, Pooja,Shinde, Sujata S.,Hong, Cho R.,Pullen, Susan M.,Reynisson, Jóhannes,Wilson, William R.,Hay, Michael P.
, p. 1310 - 1324 (2016)
The radical chemistry and cytotoxicity of a series of quinoxaline di-N-oxide (QDO) compounds has been investigated to explore the mechanism of action of this class of bioreductive drugs. A series of water-soluble 3-trifluoromethyl (4-10), 3-phenyl (11-19)
Synthesis of novel fluorobenzofuroxans by oxidation of anilines and thermal cyclization of arylazides
Leyva, Socorro,Castanedo, Víctor,Leyva, Elisa
, p. 171 - 175 (2007/10/03)
The synthesis of several fluorobenzofuroxans by oxidation of fluoroanilines and thermal cyclization of fluoroarylazides is presented. The fluorobenzofuroxans prepared in this study presented tautomerism as evidenced by their NMR data. Benzofuroxans in general have biological activity and are synthetic intermediates for the preparation of several compounds with important pharmaceutical applications.
Fluorinated Heterocycles: II. Synthesis of Quinoxaline 1,4-Dioxides
Kotovskaya,Charushin,Chupakhin,Kozhevnikova
, p. 369 - 374 (2007/10/03)
7-Amino-6-fluoroquinoxaline 1,4-dioxides have been synthesized by reaction of 5,6-difluorobenzofuroxan with enamines derived from cycloalkanones and with malononitrile. The transformation of 5,6-difluorobenzofuroxan into quinoxalin 1,4-dioxides in the pre
Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
Monge, Antonio,Palop, Juan A.,Cerain, Adela Lopez de,Senador, Virginia,Martinez-Crespo, Francisko J.,et al.
, p. 1786 - 1792 (2007/10/02)
Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy.Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy.The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells.Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and /or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells.Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced.Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxide have reduction potentials significantly more positive than Tirapazamine (Epc -0.90 V).The most potent cytotoxins to cells in culture were the 6,7-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine.The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity.Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro.In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine.This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
