From imide to lactam metallo-pyridocarbazoles: distinct scaffolds for the design of selective protein kinase inhibitors.
J Org Chem
; 74(23): 8997-9009, 2009 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-19886617
ABSTRACT
Organometallic pyridocarbazole scaffolds are investigated as protein kinase inhibitors. Whereas our previous designs employed solely a maleimide pharmacophore for achieving the two crucial canonical hydrogen bonds to the hinge region of the ATP binding site, we have now extended our investigations to include the related lactam metallo-pyridocarbazoles. The synthetic access of the two regioisomeric lactam pyridocarbazoles is described, and the distinct biological properties of the two lactam scaffolds are revealed by employing a ruthenium half sandwich complex as a model system, resulting in organometallic lead structures for the inhibition of the protein kinases TrkA and CLK2. These new lactam metallo-pyridocarbazoles expand our existing molecular toolbox and assist toward the generation of metal complex scaffolds as lead structures for the design of selective inhibitors for numerous kinases of the human kinome.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Piridonas
/
Carbazóis
/
Inibidores de Proteínas Quinases
/
Imidas
/
Lactamas
Limite:
Humans
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Alemanha