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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 ?-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.

SUBMITTER: Zimmermann SC

PROVIDER: S-EPMC4233358 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Structure-Metabolism Relationships in the Glucuronidation of d-Amino Acid Oxidase Inhibitors.

Zimmermann Sarah C SC Rais Rana R Alt Jesse J Burzynski Caitlin C Slusher Barbara S BS Tsukamoto Takashi T

ACS medicinal chemistry letters 20141021 11

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 resis ...[more]

PMID: 25408840

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