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Basic Chemistry of 2-Nitroimidazoles (Azomycin Derivatives)

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Imaging of Hypoxia

Part of the book series: Developments in Nuclear Medicine ((DNUM,volume 33))

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Abstract

2-Nitroimidazole (azomycin, 1, Fig. 1) is a naturally occurring antibiotic. Synthetic nitroimidazoles are pharmaceutically used for the treatment of infections. Metronidazole (2), a 5-nitroimidazole derivative, shows trichomonacidal activity besides activity against a wide variety of anaerobic protozoal parasites and anaerobic bacteria, including Helicobacter pylori (Hardman et al. 1996).

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References

  • Adebayo A.T.O.M., Bowman W.R., Salt W.G. SRN1 and oxidative addition of nitroimidazole anions. Tetrahedron Lett. 1986, 27, 1943–1946.

    Article  CAS  Google Scholar 

  • Agrawal K.C., Bears K.B., Sehgal R.K., Brown J.N., Rist P.E., Rupp W.D. Potential radiosensitizing agents. Dinitroimidazoles. J. Med. Chem. 1979, 22, 583–586.

    Article  PubMed  CAS  Google Scholar 

  • Beaman A.G., Tautz W., Duschinsky R. Studies in the nitroimidazole series III. 2-nitroimidazole derivatives substituted in the 1-position. Antimicrobial Agents Chemother. 1968, 520–530.

    Google Scholar 

  • Beaman A.G., Tautz W., Gabriel T., Keller O., Toome V., Duschinsky R. Studies in the nitroimidazole series I. synthesis of azomycin A and related compounds. Antimicrobial Agents Chemother. 1968b 469–477.

    Google Scholar 

  • Betageri G.V., Rogers, J.A. Correlation of partioning of nitroimidazoles in the n-octanollsaline and liposome systems with pharmacokinetic parameters and quantitative structure activity relationships (QSAR). Pharm. Res. 1989, 6, 399–403.

    Article  PubMed  CAS  Google Scholar 

  • Boyer J.H., Nitroazoles. 1986 VCH Publ. Inc., Dearfield Beach USA.

    Google Scholar 

  • Breccia A., Cavalieri B, Adams G.E. Nitroimidazoles; Chemistry, Pharmacology and Clinical Applications. Plenum Press, New York, 1982.

    Book  Google Scholar 

  • Budavari S., The Merck Index 1989 11th ed., Merck & Co. Inc., Rahway New Jersey.

    Google Scholar 

  • Catalan J., Menendez M., Elguero J. On the relationships between basicity and acidity in azoles. Bull. Soc. Chim. Fr. 1985 I-30-I-33.

    Google Scholar 

  • Cavalieri B., Ballotta R., Arioli V., Lancini G. New 5-substituted 1-alkyl-2-nitroimidazoles. J. Med. Chem. 1973, 16, 557–560.

    Article  Google Scholar 

  • Cavalieri B., Volpe G., Arioli V. Synthesis and biological activity of some vinyl-substituted 2nitroimidazoles. J. Med. Chem. 1977, 20, 656–660.

    Article  Google Scholar 

  • Cavalieri B., Volpe G., Arioli V., Pizzocheri F., Diena A. Synthesis and biological activity of new 2nitroimidazole derivatives. J. Med. Chem. 1978, 21, 781–784.

    Article  Google Scholar 

  • Cherif A., Wallace S., Yang D.J., Newman R.A., Harrod V.L., Nornoo A., Inoue T., Kim C.G., Kuang L.R., Kim E.E., Podoloff D.A. Development of new markers for hypoxic cells: [131I]Iodomisonidazole and [131I]Iodoerythronitroimidazole. J. Drug Target. 1996, 4, 31–39.

    Article  PubMed  CAS  Google Scholar 

  • Elks J, Ganellin C.R. (eds.) Dictionary of drugs. 1990. Chapman and Hall, London.

    Google Scholar 

  • Gilchrist T.L. Heterocyclic chemistry, 3rd ed. 1997, Addison Wesley Longman Ltd., Harlow, England.

    Google Scholar 

  • Hardman J.G., Limbird L.E., Molinoff P.B., Ruddon R.W., Gilman A.G. (eds) Goodman & Gilman’s The pharmacological basis of therapeutics, 9th ed., McGraw-Hill, New York 1996.

    Google Scholar 

  • Hay M.P., Wilson W.R., Moselen J.W., Palmer B.D., Denny W.A. Hypoxia-selective antitumor agents. 8. Bis(nitroimidazolyl)alkanecarboxamides: a new class of hypoxia-selective cytotoxins and hypoxic cell radiosensitisers. J. Med. Chem. 1994, 37, 381–391.

    Article  PubMed  CAS  Google Scholar 

  • Hay M.P., Lee H.H., Wilson W.R., Roberts P.B., Denny W.A. Hypoxia-selective antitumor agents. 10. bis(nitroimidazoles) and related bis(nitroheterocycles): development of derivatives with higher rates of metabolic activation under hypoxia and improved aqueous solubility. J. Med. Chem. 1995, 38, 1928–1941.

    Article  PubMed  CAS  Google Scholar 

  • Hodgkiss R.J., Jones, G.W., Long A., Middleton R.W., Parrick J., Stratford M.R.L., Wardman P., Wilson G.D. Flourescent markers for hypoxic cells: a study of nitroaromatic compounds, with fluorescent heterocyclic side chains, that undergo bioreductive binding. J. Med. Chem. 1991, 34, 2268–2274.

    Article  PubMed  CAS  Google Scholar 

  • Hodgkiss R.J., Parrick J., Porssa M, Stratford M.R. Bioreductive markers for hypoxic cells: 2nitroimidazoles with biotinylated 1-substituents. J. Med. Chem. 1994, 37, 4352–4356.

    Article  PubMed  CAS  Google Scholar 

  • Hodgkiss R.J., Middleton R.W., Parrick J., Rami H.K., Wardman P, Wilson G.D. Bioreductive fluorescent markers for hypoxic cells: a study of 2-nitroimidazoles with 1-substituents containing fluorescent, bridgehead-nitrogen, bicyclic systems. J. Med. Chem. 1992, 35, 1920–1926.

    Article  PubMed  CAS  Google Scholar 

  • Hori H., Jin C-Z., Kiyono M., Kasai S., Shimamura M., Inayama S. Design, synthesis, and biological activity of anti-angiogenic hypoxic cell radiosensitizer haloacetylcarbamoyl-2-nitroimidazoles. Bioorg. Med. Chem. 1997, 5, 591–599.

    Article  PubMed  CAS  Google Scholar 

  • Katritzky A.R. Comprehensive heterocyclic chemistry. Vol. 5. 1984, Pergamon Press Ltd., Oxford

    Google Scholar 

  • Lawton, C.A., Coleman C.N., Buzydlowskki J.W., Forman J.D., Marcial V.A., DelRowe J.D., Rotman M. Results of a phase II trial of external beam radiation with etanidazole (SR 2508) for the treatment of locally advanced prostate cancer (RTOG Protocol 90–20). Int. J. Radiat. Oncol. Biol. Phys. 1996, 36, 673–680.

    Article  PubMed  CAS  Google Scholar 

  • Linder K.E., Chan Y. W, Cyr J.E., Nowotnik D.P., Eckerlamn W.C., Nunn A.D. Synthesis, characterization, and in vitro evaluation of nitroimidazole-BATO complexes: new technetium compounds designed for imaging hypoxic tissue. Bioconjug. Chem. 1993, 4, 326–333.

    Article  PubMed  CAS  Google Scholar 

  • Linder K.E., Chan Y.W., Cyr J.E., Malley M.F., Nowotnik D.P., Nunn A.D. TcO(PnA.O-1-(2nitroimidazole)) [BMS-181321], a new technetium-containing nitroimidazole complex for imaging hypoxia: synthesis, characterization, and xanthine oxidase-catalyzed reduction. J. Med. Chem. 1994, 37, 9–17.

    Article  PubMed  CAS  Google Scholar 

  • Long A., Parrick J., Hodgkiss R.J. An efficient procedure for the 1-alkylation of 2-nitroimidazoles and the synthesis of a probe for hypoxia in solid tumours. Synthesis 1991, 709–713.

    Google Scholar 

  • Maurin M.B., Rowe S.M., Field K.S., Swintosky R.C., Hussain M.A. Solubility behavior, phase transition, and structure-based nucleation inhibition of etanidazole in aqueous solutions. Pharm. Res. 1996, 13, 1401 - 1405.

    Article  PubMed  CAS  Google Scholar 

  • McClelland R.A., Panicucci R., Rauth A.M. Products of the reductions of 2-nitroimidazoles. J. Am. Chem. Soc. 1987 109,4308–4314.

    Article  CAS  Google Scholar 

  • Murayama C, Suzuki A, Suzuki T, Miyata Y, Sakaguchi M, Tanabe Y, Tanaka N, Mori T. Radiosensitization by a new nucleoside analogue: 1-[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl-2nitroimidazole (RP-170). Int J Radiat Oncol Biol Phys, 1989, 17, 575–581.

    Article  PubMed  CAS  Google Scholar 

  • Murayama C, Suzuki A, Sato C, Tanabe Y, Miyata Y, Shoji T, Suzuki T, Sakaguchi M, Mori T. Radiosensitization by 2-nitroimidazole nucleoside analog RP-170: radiosensitizing effects under both intravenous and oral administration. Int J Radiat Oncol Biol Phys, 1992, 22, 557–560.

    Article  PubMed  CAS  Google Scholar 

  • Murayama C, Suzuki A, Sato C, Tanabe Y, Shoji T, Miyata Y, Nishio A, Suzuki T, Sakaguchi M, Mori T. Radiosensitization by a new potent nucleoside analog: 1-(1’,3’,4’-trihydroxy-2’-butoxy)methyl-2nitroimidazole(RP-343). Int J Radiat Oncol Biol Phys, 1993, 26, 433–443.

    Article  PubMed  CAS  Google Scholar 

  • Nair M.D., Nagarajan K. Nitroimidazoles as chemotherapeutic agents. In Jucker E. (ed.) Progress in drug research, 1983 27,163–255.

    Google Scholar 

  • Nunn A., Linder K., Strauss H.W. Nitroimidazoles and imaging hypoxia. Eur. J. Nucl. Med. 1995 22,265–280.

    Article  PubMed  CAS  Google Scholar 

  • Oya N., Shibamoto Y., Sasai K., Shibata T., Murata R., Takagi T., Iwai H., Suzuki T., Abe M. Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization eficiency and toxicity. Int. J. Radiat. Oncol. Biol. Phys. 1995, 33, 119–127.

    Article  PubMed  CAS  Google Scholar 

  • Palmer B.D., Denny W.A. Synthesis and reactions of brominated 2-nitroimidazoles. J. Chem. Soc. Perkin Trans. I 1989 95–99.

    Article  Google Scholar 

  • Pedersen JE, Barron G, Chapman JD. Azomycin riboside: a new radiosensitizer. Int J Radiat Oncol Biol Phys, 1982 8,415–418.

    Article  PubMed  CAS  Google Scholar 

  • Perlman M E, Dunn J.A., Piscitelli T.A., Earle J., Rose W.C., Wampler G.L., MacDiarmid J.E., Bardos T.J. Synthesis of potential dual-acting radiation sensitizer antineoplastic agents: 2,2-dimethylphosphoraziridines containing 2-nitroimidazoles or other electron-affinic moieties. J. Med. Chem. 1991, 34, 1400–1407.

    Article  PubMed  CAS  Google Scholar 

  • Ramalingam K., Raju N., Nanjappan P., Linder K.E., Pirro J., Zeng W., Rumsey W., Nowotnik D.P., Nunn A.D. The synthesis and in vitro evaluation of a 99m technetium-nitroimidazole complex based on a bis(amine-phenol) ligand: comparison to BMS-181321. J. Med. Chem. 1994, 37, 4155–4163.

    Article  PubMed  CAS  Google Scholar 

  • Rousseau R.J., Robins R.k., Townsend L.B. The synthesis of 2-nitro-l-(3-D-ribofuranosylimidazole (azomycin riboside) (1). J. Heterocycl. Chem. 1967, 4, 311–312.

    Article  CAS  Google Scholar 

  • Rumsey W.L., Kuczynski B., Patel B., Bauer A., Narra R.K., Eaton S.M., Nunn A.D., Strauss H.W. SPECT imaging of ischemic myocardium using a technetium-99m-nitroimidazole ligand. J. Nucl. Med. 1995, 36, 1445–1450.

    PubMed  CAS  Google Scholar 

  • Sakaguchi M., Larroquette C.A., Agrawal K.C. Potential radiosensitizing agents. 6. 2-Nitroimidazole nucleosides: arabinofuranosyl and hexopyranosyl analogues. J. Med. Chem. 1983 26,20–24.

    Article  PubMed  CAS  Google Scholar 

  • Sasai K, Shibamoto Y, Takahashi M, Abe M, Wang J, Zhou L, Nishimoto S, Kagiya T. A new, potent 2nitroimidazole nucleoside hypoxic cell radiosensitizer, RP170. Jpn J Cancer Res 1989, 1113–1118.

    Google Scholar 

  • Searcey M., Pye P.L., Lee J.B. Improved syntheses of N-substituted nitroimidazoles. Synth. Commun. 1989 19,1309–1315.

    Article  CAS  Google Scholar 

  • Sehgal R.K., Agrawal K.C. Hydroxymethylation and cyanomethylation of nitroimidazoles. J. Heterocycl. Chem. 1979 16,871–876.

    Article  CAS  Google Scholar 

  • Shi C.Q., Sinusas A.J., Dione D.P., Singer M.J., Young L.H., Heller E.N., Rinker B.D., Wackers F.J., Zaret B.L. Technetium-99m-nitroimidazole (BMS181321): a positive imaging agent for detecting myocardial ischemia. J. Nucl. Med. 1995, 36, 1078–1086.

    PubMed  CAS  Google Scholar 

  • Shibamoto Y, Sasai K, Sakaguchi M, Tamulevicius P, Kitakabu Y, Streffer C, Abe M. Evaluation of a new 2-nitroimidazole nucleoside analogue, RK-28 as a radiosensitizer for clinical use. Int J Radiat Biol 1991, 59, 105–115.

    Article  PubMed  CAS  Google Scholar 

  • Tautz W., Teitel S., Brossi A. Nitrohistidines and Nitrohistamines. J. Med. Chem. 1973, 16, 705–707.

    Article  PubMed  CAS  Google Scholar 

  • Theobald R.S. in Rodd’s Chemistry of Carbon Compounds, Vol. IVC, Elsevier Science Publishers B.V., Amsterdam, 1986.

    Google Scholar 

  • Townsend L.B. (ed.) Chemistry of Nucleosides and Nucleotides, Vol. 3, Plenum Press, New York, 1994.

    Google Scholar 

  • Yang DJ, Wallace S, Cherif A., Li C., Gretzer M.B., Kim E.E., Podoloff D.A. Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia. Radiology 1995, 194, 795–800.

    PubMed  CAS  Google Scholar 

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Authors
  1. Christa E. Müller
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Editors and Affiliations

  1. Section Radiopharmacy, Interdisciplinary PET-Center, Eberhard-Karls University, Tübingen, Germany

    Hans-Jürgen Machulla

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Müller, C.E. (1999). Basic Chemistry of 2-Nitroimidazoles (Azomycin Derivatives). In: Machulla, HJ. (eds) Imaging of Hypoxia. Developments in Nuclear Medicine, vol 33. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1828-8_3

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  • DOI: https://doi.org/10.1007/978-94-017-1828-8_3

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5157-8

  • Online ISBN: 978-94-017-1828-8

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