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

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). The inhibitory potency is largely dependent on the size and position of substituents on the benzene ring with IC50 values of the co...

Full description

Saved in:
Bibliographic Details
Published in:ACS medicinal chemistry letters 2012-10, Vol.3 (10), p.839-843
Main Authors: Berry, James F, Ferraris, Dana V, Duvall, Bridget, Hin, Niyada, Rais, Rana, Alt, Jesse, Thomas, Ajit G, Rojas, Camilo, Hashimoto, Kenji, Slusher, Barbara S, Tsukamoto, Takashi
Format: Article
Language:English
Subjects:
Letter
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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). The inhibitory potency is largely dependent on the size and position of substituents on the benzene ring with IC50 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. Two of these compounds were given to mice orally together with d-serine to assess their effects on plasma d-serine pharmacokinetics.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml300212a