61322-32-5Relevant academic research and scientific papers
6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Novel d -Amino Acid Oxidase Inhibitors
Hin, Niyada,Duvall, Bridget,Ferraris, Dana,Alt, Jesse,Thomas, Ajit G.,Rais, Rana,Rojas, Camilo,Wu, Ying,Wozniak, Krystyna M.,Slusher, Barbara S.,Tsukamoto, Takashi
, p. 7258 - 7272 (2015/10/05)
A series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives were synthesized as inhibitors of d-amino acid oxidase (DAAO). Many compounds in this series were found to be potent DAAO inhibitors, with IC50 values in the double-digit nanomolar range. The 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione pharmacophore appears metabolically resistant to O-glucuronidation unlike other structurally related DAAO inhibitors. Among them, 6-hydroxy-2-(naphthalen-1-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione 11h was found to be selective over a number of targets and orally available in mice. Furthermore, oral coadministration of d-serine with 11h enhanced the plasma levels of d-serine in mice compared to the oral administration of d-serine alone, demonstrating its ability to serve as a pharmacoenhancer of d-serine.
INHIBITORS OF D-AMINO ACID OXIDASE
-
Page/Page column 55, (2014/03/21)
D-amino acid oxidase (DAAO) inhibitors and methods of their use, either alone or in combination with D-serine or D-alanine, to facilitate allosteric activation of NMDA receptor-mediated neurotransmission and methods of their use as therapeutic agents for treating a subject afflicted with one or more cognitive-disorders, such as schizophrenia, including subjects suffering from negative symptoms and cognitive impairments, post-traumatic stress disorder (PTSD), or pain, are disclosed.
