Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease.
Bioorg Med Chem Lett
; 26(19): 4739-4742, 2016 10 01.
Article
em En
| MEDLINE
| ID: mdl-27568084
ABSTRACT
We report the discovery of a novel series of influenza Cap-dependent EndoNuclease (CEN) inhibitors based on the 4-pyridone-carboxylic acid (PYXA) scaffold, which were found from our chelate library. Our SAR research revealed the lipophilic domain to be the key to CEN inhibition. In particular, the position between the chelate and the lipophilic domain in the derivatives was essential for enhancing the potency. Our study, based on virtual modeling, led to the identification of 2y as a potent CEN inhibitor with an IC50 of 5.12nM.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Orthomyxoviridae
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Piridonas
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Endonucleases
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Inibidores Enzimáticos
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Descoberta de Drogas
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article