Discovery of imidazo[1,2-b]pyridazines as IKKß inhibitors. Part 2: improvement of potency in vitro and in vivo.
Bioorg Med Chem Lett
; 21(3): 904-8, 2011 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-21232950
ABSTRACT
We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKß inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKß by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds showed inhibitory activity of TNFα production in mice.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridazinas
/
Inibidores de Proteínas Quinases
/
Quinase I-kappa B
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Japão