title: Structure-Metabolism Relationships in the Glucuronidation of d-Amino Acid Oxidase Inhibitors.
abstract: Representative d-amino acid oxidase (DAAO) inhibitors were subjected to in vitro liver microsomal stability tests in the absence or presence of uridine diphosphate glucuronic acid (UDPGA). While carboxylate-based DAAO inhibitors displayed little glucuronidation, most DAAO inhibitors containing α-hydroxycarbonyl moiety exhibited nearly complete glucuronidation within 30 min. The one exception was 6-[2-(3,5-difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one 10, which exhibited some degree of resistance to glucuronidation by liver microsomes from mice, rats, and humans.
authors.affiliation: Department of Neurology and Brain Science Institute, Johns Hopkins University , Baltimore, Maryland 21205, United States.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Zimmermann
authors.affiliation: Department of Neurology and Brain Science Institute, Johns Hopkins University , Baltimore, Maryland 21205, United States.
authors.forename: Rana
authors.initials: R
authors.lastname: Rais
authors.affiliation: Department of Neurology and Brain Science Institute, Johns Hopkins University , Baltimore, Maryland 21205, United States.
authors.forename: Jesse
authors.initials: J
authors.lastname: Alt
authors.affiliation: Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse-Intramural Research Program , Baltimore, Maryland 21224, United States.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Burzynski
authors.affiliation: Department of Neurology and Brain Science Institute, Johns Hopkins University , Baltimore, Maryland 21205, United States.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Slusher
authors.affiliation: Department of Neurology and Brain Science Institute, Johns Hopkins University , Baltimore, Maryland 21205, United States.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsukamoto
keywords: d-amino acid oxidase (DAAO); drug metabolism; glucuronidation