Phenylindenone isomers as divergent modulators of p38α MAP kinase.
Bioorg Med Chem Lett
; 26(21): 5160-5163, 2016 11 01.
Article
em En
| MEDLINE
| ID: mdl-27746002
ABSTRACT
Two new fluorophenylindenone derivatives were designed as potential p38α MAPK modulators by preserving the key interactions of the vicinal pyridine/fluorophenyl pharmacophore with the enzyme protein. Interestingly, these two fluorophenylindenone isomers showed divergent activities, with compound 6 behaving as an inhibitor and 5 as a putative activator. These results were rationalized by docking studies and molecular dynamics simulations in terms of stabilization of DFG loop, by compound 5 in a conformation more accessible to phosphorylation.
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MEDLINE
Assunto principal:
Fenindiona
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Proteínas Quinases p38 Ativadas por Mitógeno
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article