Synthesis and SAR of 1-Hydroxy-1H-benzo[d]imidazol-2(3H)-ones as Inhibitors of d-Amino Acid Oxidase
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- 作者：James F. Berry ; Dana V. Ferraris ; Bridget Duvall ; Niyada Hin ; Rana Rais ; Jesse Alt ; Ajit G. Thomas ; Camilo Rojas ; Kenji Hashimoto ; Barbara S. Slusher ; Takashi Tsukamoto
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：October 11, 2012
- 年：2012
- 卷：3
- 期：10
- 页码：839-843
- 全文大小：271K
- 年卷期：v.3,no.10(October 11, 2012)
- ISSN：1948-5875
文摘
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 渭M. Structure鈥揳ctivity 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.