Discovery and analgesic evaluation of 8-chloro-1,4-dihydropyrido[2,3- b ]pyrazine-2,3-dione as a novel potent d -amino acid oxidase inhibitor

Dongsheng Xie, Jun Lu, Jin Xie, Junjun Cui, Teng Fei Li, Yan Chao Wang, Yuan Chen, Nian Gong, Xin Yan Li, Lei Fu, Yong Xiang Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


A series of 5-azaquinoxaline-2,3-dione derivatives were synthesized and evaluated on d-amino acid oxidase (DAAO) inhibition as potential α-hydroxylactam-based inhibitors. The potent inhibitory activities in vitro suggested that 5-nitrogen could significantly enhance the binding affinity by strengthening relevant hydrogen bond interactions. The analgesic effects of intrathecal and systemic injection of 8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione, a representative molecule of 5-azaquinoxaline-2,3-dione, were investigated in rodents. This research not only confirmed the analgesic effect of the DAAO inhibitors but provided a new class of chemical entities with oral application potential for the treatment of chronic pain and morphine analgesic tolerance.

Original languageEnglish
Pages (from-to)19-32
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 19 Jul 2016
Externally publishedYes


  • 5-Azaquinoxaline-2,3-diones
  • 8-Chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione
  • Analgesic effects
  • D-amino acid oxidase
  • DAAO inhibitors

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