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Synthesis, Crystal Structure, and Rotational Energy Profile of 3-Cyclopropyl-1,2,4-benzotriazine 1,4-Di-N-oxide

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Abstract

1,2,4-Benzotriazine 1,4-di-N-oxides are potent antitumor drug candidates that undergo in vivo bioreduction leading to selective DNA damage in the low oxygen (hypoxic) cells found in tumors. Tirapazamine (TPZ) is the lead compound in this family. Here we report on the synthesis, crystal structure, and conformational analysis of a new analog, 3-cyclopropyl-1,2,4-benzotriazine 1,4-di-N-oxide (3). Compound 3 (C10H10N3O2) crystallized in the monoclinic space group C2/c. Unit cell parameters for 3: a = 16.6306 (12), b = 7.799 (5), c = 16.0113 (11) Å, α = 90, β = 119.0440 (10), γ = 90, and z = 8.

Graphical Abstract

1,2,4-Benzotriazine 1,4-di-N-oxides are antitumor drug candidates that undergo in vivo bioreduction to yield DNA-damaging radical intermediates in hypoxic tumor cells. Here we report on the synthesis, crystal structure, and conformational analysis of a new analog, 3-cyclopropyl-1,2,4-benzotriazine 1,4-di-N-oxide (3).

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Acknowledgments

We thank National Institutes of Health (CA 100757) for support of this work. MU Research Computing is supported by Federal Earmark NASA Funds for Bioinformatics Consortium Equipment and additional support from Dell, SGI, Sun Microsystems, TimeLogic and Intel.

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Authors and Affiliations

  1. Department of Chemistry, 125 Chemistry Building, University of Missouri-Columbia, Columbia, MO, 65211, USA

    Ujjal Sarkar, Rainer Glaser, Zack D. Parsons, Charles L. Barnes & Kent S. Gates

  2. Department of Biochemistry, University of Missouri-Columbia, Columbia, MO, 65211, USA

    Kent S. Gates

Authors
  1. Ujjal Sarkar
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  2. Rainer Glaser
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  3. Zack D. Parsons
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  4. Charles L. Barnes
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  5. Kent S. Gates
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Correspondence to Kent S. Gates.

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Sarkar, U., Glaser, R., Parsons, Z.D. et al. Synthesis, Crystal Structure, and Rotational Energy Profile of 3-Cyclopropyl-1,2,4-benzotriazine 1,4-Di-N-oxide. J Chem Crystallogr 40, 624–629 (2010). https://doi.org/10.1007/s10870-010-9707-9

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  • DOI: https://doi.org/10.1007/s10870-010-9707-9

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