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

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

  • ACS Med Chem Lett. 2012 Oct 11;3(10):839-843. doi: 10.1021/ml300212a.
James F Berry 1,  Dana V Ferraris,  Bridget Duvall,  Niyada Hin,  Rana Rais,  Jesse Alt,  Ajit G Thomas,  Camilo Rojas,  Kenji Hashimoto,  Barbara S Slusher,  Takashi Tsukamoto
Affiliations

Affiliation

  • 1 Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, United States.
PMID: 23243487 DOI: 10.1021/ml300212a
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.

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