title: 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.
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, United States.
authors.forename: James F
authors.initials: JF
authors.lastname: Berry
authors.forename: Dana V
authors.initials: DV
authors.lastname: Ferraris
authors.forename: Bridget
authors.initials: B
authors.lastname: Duvall
authors.forename: Niyada
authors.initials: N
authors.lastname: Hin
authors.forename: Rana
authors.initials: R
authors.lastname: Rais
authors.forename: Jesse
authors.initials: J
authors.lastname: Alt
authors.forename: Ajit G
authors.initials: AG
authors.lastname: Thomas
authors.forename: Camilo
authors.initials: C
authors.lastname: Rojas
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Slusher
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsukamoto