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Synthesis and SAR of 1-hydroxy-1H-benzo[d]imidazol-2(3H)-ones as Inhibitors of D-Amino Acid Oxidase.

ABSTRACT: A series of 1-hydroxy-1H-benzo[d]imidazol-2(3H)-ones were synthesized and evaluated for their ability to inhibit human and porcine forms of D-amino acid oxidase (DAAO). Inhibitory potency is largely dependent on the size and position of substituents on the benzene ring with IC(50) values of the compounds ranging from 70 nM to greater than 100 µM. Structure-activity relationships of this new class of DAAO inhibitors will be presented in detail along with comparisons to previously published SAR data from other classes of DAAO inhibitors. Some of these compounds were given to mice orally together with D-serine to assess their effects on plasma D-serine pharmacokinetics.

SUBMITTER: Berry JF

PROVIDER: S-EPMC3519437 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Synthesis and SAR of 1-hydroxy-1H-benzo[d]imidazol-2(3H)-ones as Inhibitors of D-Amino Acid Oxidase.

Berry James F JF Ferraris Dana V DV Duvall Bridget B Hin Niyada N Rais Rana R Alt Jesse J Thomas Ajit G AG Rojas Camilo C Hashimoto Kenji K Slusher Barbara S BS Tsukamoto Takashi T

ACS medicinal chemistry letters 20120916 10

A series of 1-hydroxy-1H-benzo[d]imidazol-2(3H)-ones were synthesized and evaluated for their ability to inhibit human and porcine forms of D-amino acid oxidase (DAAO). Inhibitory potency is largely dependent on the size and position of substituents on the benzene ring with IC(50) values of the compounds ranging from 70 nM to greater than 100 µM. Structure-activity relationships of this new class of DAAO inhibitors will be presented in detail along with comparisons to previously published SAR da ...[more]

PMID: 23243487

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