2-Carbaborane-3-phenyl-1H-indoles—Synthesis via McMurry Reaction and Cyclooxygenase (COX) Inhibition Activity

Authors

  • Markus Laube,

    Corresponding author
    1. Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328 Dresden (Germany)
    2. Fachrichtung Chemie und Lebensmittelchemie, Technische Universität Dresden, 01062 Dresden (Germany)
    • Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328 Dresden (Germany)
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  • Wilma Neumann,

    1. Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig (Germany)
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  • Dr. Matthias Scholz,

    1. Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig (Germany)
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  • Dr. Peter Lönnecke,

    1. Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig (Germany)
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  • Brenda Crews,

    1. Department of Biochemistry, Vanderbilt Institute for Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 (USA)
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  • Prof. Dr. Lawrence J. Marnett,

    1. Department of Biochemistry, Vanderbilt Institute for Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 (USA)
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  • Prof. Dr. Jens Pietzsch,

    1. Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328 Dresden (Germany)
    2. Fachrichtung Chemie und Lebensmittelchemie, Technische Universität Dresden, 01062 Dresden (Germany)
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  • Dr. Torsten Kniess,

    1. Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328 Dresden (Germany)
    2. Fachrichtung Chemie und Lebensmittelchemie, Technische Universität Dresden, 01062 Dresden (Germany)
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  • Prof. Dr. Evamarie Hey-Hawkins

    Corresponding author
    1. Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig (Germany)
    • Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig (Germany)
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Abstract

Cyclooxygenase-2 (COX-2) inhibitors have been the focus of medicinal chemistry efforts for years, and many compounds that exhibit high selectivity and affinity have been developed. As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development, this paper presents the synthesis of carbaboranyl derivatives of COX-2-selective 2,3-disubstituted indoles. Despite the lability of carbaboranes under reducing conditions, 2-carbaborane-3-phenyl-1H-indoles could be synthesized by McMurry cyclization of the corresponding amides. Whereas the meta-carbaboranyl-substituted derivatives lacked COX inhibitory activity, an ortho-carbaboranyl analogue was active, but showed a selectivity shift toward COX-1.

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