Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors.
Bioorg Med Chem Lett
; 23(21): 5923-30, 2013 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-24042009
ABSTRACT
A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Inibidores de Proteínas Quinases
/
Janus Quinase 1
/
Janus Quinase 2
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article