What question did this study set out to answer?

August 26, 2015Journal of Medicinal ChemistryOpen Access

6-Hydroxy-1,2,4-triazine-3,5(2 H ,4 H )-dione Derivatives as Novel d -Amino Acid Oxidase Inhibitors

View Full Paper

Ask AI

Bookmark

Authors

NHNiyada HinJohns Hopkins University BDBridget DuvallJohns Hopkins University DFDana FerrarisMcDaniel College

Discussion

Member takes

Implication

Preclinical evaluation demonstrates potent D-amino acid oxidase inhibition and enhanced plasma D-serine levels in mice, indicating therapeutic potential as a metabolic pharmacoenhancer.

Key Points

To synthesize and evaluate a series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives as novel and metabolically stable D-amino acid oxidase (DAAO) inhibitors.
Synthesized 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives and measured in vitro inhibitory potencies against D-amino acid oxidase.
Assessed metabolic resistance to O-glucuronidation and evaluated selectivity profiles against alternative biological targets.
Administered lead compound 11h orally with or without D-serine in mice to determine oral bioavailability and pharmacokinetic enhancement of plasma D-serine levels.
Multiple derivatives exhibited potent DAAO inhibition with IC50 values in the double-digit nanomolar range and maintained resistance to O-glucuronidation.
Compound 11h displayed broad target selectivity and high oral bioavailability in murine models.
Oral coadministration of compound 11h alongside D-serine significantly elevated plasma D-serine concentrations compared to D-serine administration alone.

Cite This Study

Hin et al. (2015) studied this question.

synapsesocial.com/papers/6a9a0c956bb205df309e469d https://doi.org/10.1021/acs.jmedchem.5b00482

View Full Paper

Ask AI

Bookmark

Implication

Preclinical evaluation demonstrates potent D-amino acid oxidase inhibition and enhanced plasma D-serine levels in mice, indicating therapeutic potential as a metabolic pharmacoenhancer.

6-Hydroxy-1,2,4-triazine-3,5(2 H ,4 H )-dione Derivatives as Novel d -Amino Acid Oxidase Inhibitors

Discussion

Member takes

Implication

Key Points

Cite This Study

6-Hydroxy-1,2,4-triazine-3,5(2 H ,4 H )-dione Derivatives as Novel d -Amino Acid Oxidase Inhibitors

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider