Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes.
Bioorg Med Chem Lett
; 15(23): 5274-9, 2005 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-16169718
ABSTRACT
Two new classes of diphenylether inhibitors of p38alpha MAP kinase are described. Both chemical classes are based on a common diphenylether core that is identified by simulated fragment annealing as one of the most favored chemotypes within a prominent hydrophobic pocket of the p38alpha ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make specific interactions with either the adenine binding site or the phosphate binding site of ATP. The synthesis, crystallographic analysis, and biological activity of these p38alpha inhibitors are discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Bifenilo
/
Proteína Quinase 14 Ativada por Mitógeno
/
Inibidores de Proteínas Quinases
/
Éteres
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos