Structure-metabolism relationships in the glucuronidation of d-amino acid oxidase inhibitors

Sarah C. Zimmermann, Rana Rais, Jesse Alt, Caitlin Burzynski, Barbara S. Slusher, Takashi Tsukamoto

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1251-1253
Number of pages3
JournalACS Medicinal Chemistry Letters
Volume5
Issue number11
DOIs
StatePublished - Nov 13 2014

Keywords

  • d -amino acid oxidase (DAAO)
  • drug metabolism
  • glucuronidation

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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