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Nitrogen Inversion Barriers Affect the N-Oxidation of Tertiary Alkylamines by Cytochromes P450

Authors

  • Dr. Patrik Rydberg,

    1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen (Denmark)
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  • Martin S. Jørgensen,

    1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen (Denmark)
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  • Dr. Thomas A. Jacobsen,

    1. Aniona, Pederstrupvej 93, 2750 Ballerup (Denmark)
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  • Dr. Anne-Marie Jacobsen,

    1. Department of Drug Metabolism, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby (Denmark)
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  • Dr. Kim G. Madsen,

    1. ADME Department, Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv (Denmark)
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  • Dr. Lars Olsen

    Corresponding author
    1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen (Denmark)
    • Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen (Denmark)
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  • This work was supported by a grant from Lhasa Limited.

Abstract

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Berechnet: Cytochrom-P450-Enzyme erleichtern verschiedenste Reaktionen. So können z. B. Amine entweder N-dealkyliert oder N-oxidiert werden – aber es ist schwierig zu begründen, welche dieser konkurrierenden Reaktionen stattfindet. Die Inversionsbarriere des Alkylamin-Stickstoffatoms scheint entscheidend für den Anteil an N-oxidiertem Produkt zu sein, der relativ zu Dealkylierungs- und Hydroxylierungsprodukten gebildet wird.

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