Amide-based inhibitors of p38alpha MAP kinase. Part 2: design, synthesis and SAR of potent N-pyrimidyl amides.
Bioorg Med Chem Lett
; 20(8): 2560-3, 2010 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-20346659
ABSTRACT
Optimization of a tri-substituted N-pyridyl amide led to the discovery of a new class of potent N-pyrimidyl amide based p38alpha MAP kinase inhibitors. Initial SAR studies led to the identification of 5-dihydrofuran as an optimal hydrophobic group. Additional side chain modifications resulted in the introduction of hydrogen bond interactions. Through extensive SAR studies, analogs bearing free amino groups and alternatives to the parent (S)-alpha-methyl benzyl moiety were identified. These compounds exhibited improved cellular activities and maintained balance between p38alpha and CYP3A4 inhibition.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Inibidores de Proteínas Quinases
/
Amidas
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos