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

doi:10.1021/ml500335z

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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 language	English (US)
Pages (from-to)	1251-1253
Number of pages	3
Journal	ACS Medicinal Chemistry Letters
Volume	5
Issue number	11
DOIs	https://doi.org/10.1021/ml500335z
State	Published - 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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10.1021/ml500335z

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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.",

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AU - Zimmermann, Sarah C.

AU - Rais, Rana

AU - Alt, Jesse

AU - Burzynski, Caitlin

AU - Slusher, Barbara S.

AU - Tsukamoto, Takashi

PY - 2014/11/13

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AB - 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.

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KW - drug metabolism

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

Abstract

Keywords

ASJC Scopus subject areas

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