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.
Eur J Med Chem
; 117: 19-32, 2016 Jul 19.
Article
em En
| MEDLINE
| ID: mdl-27089209
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinoxalinas
/
D-Aminoácido Oxidase
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Inibidores Enzimáticos
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Analgésicos
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China