General Approach To Access Aldehyde Oxidase Metabolites of Drug Molecules via N-Oxidation/Reissert-Henze-Type
Christopher M Hanneman1, Sanghoon Song1, Nicholas P R Onuska2
1Department of Chemistry, University of Wisconsin─Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
Abstract:
Aldehyde oxidase (AO) contributes significantly to metabolism of drug molecules containing heteroaromatics, and the lack of synthetic mimics for AO-mediated reactivity is a barrier to drug development. Herein, we use tandem N-oxidation and Reissert-Henze-type reaction of quinoline and related heteroaromatics to form quinolone derivatives. This reactivity is showcased with small molecule building blocks and active pharmaceutical ingredients with known AO metabolism. The products of the latter substrates map directly onto established AO metabolites.
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