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Chemical Compound Review

Quinazine     quinoxaline

Synonyms: Chinoxalin, Phenpiazine, QUINOXALINE, Phenopiazine, Benzopyrazine, ...
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Disease relevance of quinoxaline


Psychiatry related information on quinoxaline

  • Most of the quinoxaline ureas and quinoxalin-4-ones were active in an acute electroshock physical dependence side effect assay in mice precluding further development [6].
  • [Chemical reaction: see text] HOF.CH3CN, a very efficient oxygen-transfer agent made readily from fluorine and aqueous acetonitrile, was reacted with various quinoxaline derivatives to give the corresponding mono N-oxides and especially the N,N'-dioxides in very good yields under mild conditions and short reaction times [7].

High impact information on quinoxaline

  • The two planar quinoxaline rings of triostin A bis intercalate on the minor groove of the DNA double helix surrounding the CG base pairs at either end [8].
  • Bilateral microinfusion of 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.25-0.75 micrograms/0.5 microliters), 6-cyano-7-nitroquinoxaline (CNQX, 0.75-1.5 micrograms), and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(F) quinoxaline (NBQX, 0.2-1.0 micrograms) markedly stimulated food intake immediately following infusion, in a dose-dependent manner [9].
  • Stereochemistry of quinoxaline antagonist binding to a glutamate receptor investigated by Fourier transform infrared spectroscopy [10].
  • XK469, a synthetic quinoxaline phenoxypropionic acid derivative, has been found to have selective activity against a broad panel of solid tumors including several drug-resistant cell lines and has been approved for phase I clinical evaluation [11].
  • OBJECTIVES: To investigate the genotypic and phenotypic effects of in vitro resistance selection with lamivudine and/or the second generation non-nucleoside reverse transcriptase inhibitor (NNRTI) quinoxaline HBY097 using HIV-1 isolates carrying the multi-nucleoside resistance pattern linked to the Q151M mutation [12].

Chemical compound and disease context of quinoxaline

  • A series of pyrazine and quinoxaline derivatives have been synthesized, and their activity against M. tuberculosis (Mtb) and Mycobacterium avium (MAC) are reported [13].
  • A series of quinoxaline analogs of the herbicide Assure was found to have selective cytotoxicity for solid tumors of mice in a disk-diffusion-soft-agar-colony-formation-assay compared to L1210 leukemia [14].
  • Photosensitization of guanine-specific DNA damage by a cyano-substituted quinoxaline di-N-oxide [15].
  • In vitro resistance of HIV-1 against high levels of HBY 097 ((S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydro-quinoxaline-2(1H)-thione) and other quinoxaline nonnucleoside reverse transcriptase inhibitors (NNRTIs) is characterized by a specific amino acid substitution in the reverse transcriptase (RT), Gly 190Glu [16].
  • The non-NMDA antagonists NBQX (2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f) quinoxaline) and GYKI 52466 (1-(amino)phenyl-4-methyl-7,8-methylendioxy-5H-2,3,benzodiazepine. HCl) co-injected (24 nmol/microliters) with EAAs or given as i.v. infusion (30 mg/kg/3h), protected against KA toxicity in CA1, CA2 and DG cells, with no protection in CA3 and CA4 [17].

Biological context of quinoxaline


Anatomical context of quinoxaline

  • The inhibitory potencies at excitatory amino acid (EAA) receptors of 11 quinoxaline derivatives were evaluated in two-electrode voltage-clamp recordings of Xenopus oocytes injected with rat cortex mRNA [23].
  • The inhibitory effects of the six quinoxaline derivatives most potent in the Xenopus oocyte experiments were also tested against the excitatory postsynaptic field potential (EPSFP) recorded in the pyramidal cell dendritic field of the CA1 region of hippocampal slices after stimulation of the Schaffer collateral-commissural pathways [23].
  • Preincubation of HT29 cells with an alpha-2 adrenergic agonist resulted in a parallel rightward shift in the subsequent dose-response curve to 5-bromo-6-[2-imidazoline-2-yl-amino] quinoxaline (an alpha-2 adrenergic agonist) in inhibiting vasoactive intestinal peptide-stimulated cyclic AMP production [24].
  • All amino acid constituents of echinomycin as well as tryptophan, a putative precursor of the quinoxaline chromophores, are actively incorporated into echinomycin by protoplasts and resting cells, but not with equal efficiency [25].
  • DNA damage induced by a quinoxaline 1,4-di-N-oxide derivative (hypoxic selective agent) in Caco-2 cells evaluated by the comet assay [26].

Associations of quinoxaline with other chemical compounds

  • Two echinomycins are found to bind cooperatively to each DNA duplex at the CpG steps, with the two quinoxaline rings of each echinomycin bisintercalating between the C.G and A.T base pairs [27].
  • The reactivity of the 160 bp tyrT DNA fragment towards diethyl pyrocarbonate (DEPC) has been investigated in the presence of bis-intercalating quinoxaline antibiotics and the synthetic depsipeptide TANDEM [28].
  • Loviride (an alpha-APA derivative) and HBY 097 (a quinoxaline derivative) are two potent non-nucleoside RT inhibitors (NNRTIs) that have been used in human clinical trials [29].
  • Currents activated by kainate or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) in Xenopus oocytes were inhibited competitively by all the quinoxaline derivatives, with apparent Ki values ranging from 0.27 to 300 microM against kainate and from 0.25 to 137 microM against AMPA [23].
  • Furthermore, the kite conformation is more preferred in solvents with substantial hydrogen-bonding acidity: weak hydrogen-bonding interactions between the mildly basic quinoxaline and pyrazine nitrogen atoms and solvent molecules are more efficient in the open kite than in the closed vase form [30].

Gene context of quinoxaline

  • One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation [31].
  • Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively [32].
  • In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of quinoxaline derivatives [33].
  • OBJECTIVE: Tyrphostin AGL-2043 is a potent tricyclic quinoxaline inhibitor of PDGF beta-receptor tyrosine kinase (PTK), Kit, and Flt3 [34].
  • Monoclonal mouse IgG1 and IgG3 antibodies were developed to the food mutagens, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,4-f] quinoxaline (4,8-DiMeIQx) in order to make specific and sensitive detection and purification systems suitable for biological samples [35].

Analytical, diagnostic and therapeutic context of quinoxaline


  1. Carcinogenic action of quinoxaline 1,4-dioxide in rats. Tucker, M.J. J. Natl. Cancer Inst. (1975) [Pubmed]
  2. Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. Kleim, J.P., Rösner, M., Winkler, I., Paessens, A., Kirsch, R., Hsiou, Y., Arnold, E., Riess, G. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Induction of apoptosis and inhibition of small cell lung cancer growth by the quinoxaline tyrphostins. Krystal, G.W., Carlson, P., Litz, J. Cancer Res. (1997) [Pubmed]
  4. Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720. Balzarini, J., Karlsson, A., Meichsner, C., Paessens, A., Riess, G., De Clercq, E., Kleim, J.P. J. Virol. (1994) [Pubmed]
  5. Effect of phosphate and amino acids on echinomycin biosynthesis by Streptomyces echinatus. Formica, J.V., Waring, M.J. Antimicrob. Agents Chemother. (1983) [Pubmed]
  6. 3-Phenyl-substituted imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas that have high affinity at the GABAA/benzodiazepine receptor complex. Jacobsen, E.J., Stelzer, L.S., Belonga, K.L., Carter, D.B., Im, W.B., Sethy, V.H., Tang, A.H., VonVoigtlander, P.F., Petke, J.D. J. Med. Chem. (1996) [Pubmed]
  7. A new efficient route for the formation of quinoxaline N-oxides and N,N'-dioxides using HOF.CH3CN. Carmeli, M., Rozen, S. J. Org. Chem. (2006) [Pubmed]
  8. The molecular structure of a DNA-triostin A complex. Wang, A.H., Ughetto, G., Quigley, G.J., Hakoshima, T., van der Marel, G.A., van Boom, J.H., Rich, A. Science (1984) [Pubmed]
  9. Glutamate receptors in the nucleus accumbens shell control feeding behavior via the lateral hypothalamus. Maldonado-Irizarry, C.S., Swanson, C.J., Kelley, A.E. J. Neurosci. (1995) [Pubmed]
  10. Stereochemistry of quinoxaline antagonist binding to a glutamate receptor investigated by Fourier transform infrared spectroscopy. Madden, D.R., Thiran, S., Zimmermann, H., Romm, J., Jayaraman, V. J. Biol. Chem. (2001) [Pubmed]
  11. Induction of apoptosis by the new anticancer drug XK469 in human ovarian cancer cell lines. Ding, Z., Zhou, J.Y., Wei, W.Z., Baker, V.V., Wu, G.S. Oncogene (2002) [Pubmed]
  12. Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype. Van Laethem, K., Witvrouw, M., Pannecouque, C., Van Remoortel, B., Schmit, J.C., Esnouf, R., Kleim, J.P., Balzarini, J., Desmyter, J., De Clercq, E., Vandamme, A.M. AIDS (2001) [Pubmed]
  13. Synthesis and antimycobacterial activity of pyrazine and quinoxaline derivatives. Seitz, L.E., Suling, W.J., Reynolds, R.C. J. Med. Chem. (2002) [Pubmed]
  14. Preclinical antitumor efficacy of analogs of XK469: sodium-(2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]propionate. Corbett, T.H., LoRusso, P., Demchick, L., Simpson, C., Pugh, S., White, K., Kushner, J., Polin, L., Meyer, J., Czarnecki, J., Heilbrun, L., Horwitz, J.P., Gross, J.L., Behrens, C.H., Harrison, B.A., McRipley, R.J., Trainor, G. Investigational new drugs. (1998) [Pubmed]
  15. Photosensitization of guanine-specific DNA damage by a cyano-substituted quinoxaline di-N-oxide. Fuchs, T., Gates, K.S., Hwang, J.T., Greenberg, M.M. Chem. Res. Toxicol. (1999) [Pubmed]
  16. In vitro selection for different mutational patterns in the HIV-1 reverse transcriptase using high and low selective pressure of the nonnucleoside reverse transcriptase inhibitor HBY 097. Kleim, J.P., Winkler, I., Rösner, M., Kirsch, R., Rübsamen-Waigmann, H., Paessens, A., Riess, G. Virology (1997) [Pubmed]
  17. Non-NMDA antagonists protect against kainate more than AMPA toxicity in the rat hippocampus. Moncada, C., Arvin, B., Le Peillet, E., Meldrum, B.S. Neurosci. Lett. (1991) [Pubmed]
  18. DNA sequence specificity for topoisomerase II poisoning by the quinoxaline anticancer drugs XK469 and CQS. Gao, H., Yamasaki, E.F., Chan, K.K., Shen, L.L., Snapka, R.M. Mol. Pharmacol. (2003) [Pubmed]
  19. Quinoxaline 1,4-dioxide: a versatile scaffold endowed with manifold activities. Carta, A., Corona, P., Loriga, M. Current medicinal chemistry. (2005) [Pubmed]
  20. Synthesis and antitumor properties of N-[2-(dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines: a new class of putative topoisomerase inhibitors. Deady, L.W., Kaye, A.J., Finlay, G.J., Baguley, B.C., Denny, W.A. J. Med. Chem. (1997) [Pubmed]
  21. Identification of a quinoxaline derivative that is a potent telomerase inhibitor leading to cellular senescence of human cancer cells. Kim, J.H., Kim, J.H., Lee, G.E., Kim, S.W., Chung, I.K. Biochem. J. (2003) [Pubmed]
  22. Chemistry and toxicology of quinoxaline, organotin, organofluorine, and formamidine acaricides. Knowles, C.O. Environ. Health Perspect. (1976) [Pubmed]
  23. Quinoxaline derivatives: structure-activity relationships and physiological implications of inhibition of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated currents and synaptic potentials. Randle, J.C., Guet, T., Bobichon, C., Moreau, C., Curutchet, P., Lambolez, B., de Carvalho, L.P., Cordi, A., Lepagnol, J.M. Mol. Pharmacol. (1992) [Pubmed]
  24. Desensitization of the alpha-2 adrenergic receptor in HT29 and opossum kidney cell lines. Jones, S.B., Leone, S.L., Bylund, D.B. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
  25. Studies on antibiotic biosynthesis by protoplasts and resting cells of Streptomyces echinatus. Part I. The synthesis of echinomycin. Gauvreau, D., Waring, M.J. Can. J. Microbiol. (1984) [Pubmed]
  26. DNA damage induced by a quinoxaline 1,4-di-N-oxide derivative (hypoxic selective agent) in Caco-2 cells evaluated by the comet assay. Azqueta, A., Pachón, G., Cascante, M., Creppy, E.E., López de Cerain, A. Mutagenesis (2005) [Pubmed]
  27. Unstable Hoogsteen base pairs adjacent to echinomycin binding sites within a DNA duplex. Gilbert, D.E., van der Marel, G.A., van Boom, J.H., Feigon, J. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  28. Diethyl pyrocarbonate can detect a modified DNA structure induced by the binding of quinoxaline antibiotics. Portugal, J., Fox, K.R., McLean, M.J., Richenberg, J.L., Waring, M.J. Nucleic Acids Res. (1988) [Pubmed]
  29. The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. Hsiou, Y., Ding, J., Das, K., Clark, A.D., Boyer, P.L., Lewi, P., Janssen, P.A., Kleim, J.P., Rösner, M., Hughes, S.H., Arnold, E. J. Mol. Biol. (2001) [Pubmed]
  30. Conformational behavior of pyrazine-bridged and mixed-bridged cavitands: a general model for solvent effects on thermal "vase-kite" switching. Roncucci, P., Pirondini, L., Paderni, G., Massera, C., Dalcanale, E., Azov, V.A., Diederich, F. Chemistry (Weinheim an der Bergstrasse, Germany) (2006) [Pubmed]
  31. One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation. Li, J., Chen, J., Zhang, L., Wang, F., Gui, C., Zhang, L., Qin, Y., Xu, Q., Liu, H., Nan, F., Shen, J., Bai, D., Chen, K., Shen, X., Jiang, H. Bioorg. Med. Chem. (2006) [Pubmed]
  32. Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors. Iwashita, A., Hattori, K., Yamamoto, H., Ishida, J., Kido, Y., Kamijo, K., Murano, K., Miyake, H., Kinoshita, T., Warizaya, M., Ohkubo, M., Matsuoka, N., Mutoh, S. FEBS Lett. (2005) [Pubmed]
  33. Syntheses and structure-activity relationships of 5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-quinoxaline derivatives with retinoic acid receptor alpha agonistic activity. Kikuchi, K., Hibi, S., Yoshimura, H., Tokuhara, N., Tai, K., Hida, T., Yamauchi, T., Nagai, M. J. Med. Chem. (2000) [Pubmed]
  34. Tyrphostin AGL-2043 eluting stent reduces neointima formation in porcine coronary arteries. Banai, S., Gertz, S.D., Gavish, L., Chorny, M., Perez, L.S., Lazarovichi, G., Ianculuvich, M., Hoffmann, M., Orlowski, M., Golomb, G., Levitzki, A. Cardiovasc. Res. (2004) [Pubmed]
  35. Antibodies to the food mutagens, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline: useful for immunoassay and immunoaffinity chromatography of biological samples. Dragsted, L.O., Grivas, S., Frandsen, H., Larsen, J.C. Carcinogenesis (1995) [Pubmed]
  36. Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. Pelemans, H., Esnouf, R., Dunkler, A., Parniak, M.A., Vandamme, A.M., Karlsson, A., De Clercq, E., Kleim, J.P., Balzarini, J. J. Virol. (1997) [Pubmed]
  37. Preparation and DNA-binding properties of substituted triostin antibiotics. Cornish, A., Fox, K.R., Waring, M.J. Antimicrob. Agents Chemother. (1983) [Pubmed]
  38. Structural characterization of quinoxaline homopolymers and quinoxaline/ether sulfone copolymers by matrix-assisted laser desorption ionization mass spectrometry. Polce, M.J., Klein, D.J., Harris, F.W., Modarelli, D.A., Wesdemiotis, C. Anal. Chem. (2001) [Pubmed]
  39. The assay of methylglyoxal in biological systems by derivatization with 1,2-diamino-4,5-dimethoxybenzene. McLellan, A.C., Phillips, S.A., Thornalley, P.J. Anal. Biochem. (1992) [Pubmed]
  40. Separation of quinoxaline antibiotics by coil planet centrifugation. Sutherland, I.A., Lee, J.S., Gauvreau, D.J. Anal. Biochem. (1978) [Pubmed]
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