Contribution of indazolinone tautomers to kinase activity.
Bioorg Med Chem Lett
; 22(14): 4502-5, 2012 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-22738639
ABSTRACT
The design and synthesis of indazolinone containing kinase inhibitors are reported. Regioisomers that showed profound potency variation in previously-reported isoindolinone and aminoindazole systems were surprisingly found to have similar potencies in the case of the indazolinone chemical series. An interpretation using differential hinge hydrogen bonding and tautomeric equilibrium of indazolinone ring system is supported by quantum mechanics calculations. The equipotent inhibition of a representative kinase (KDR) by regioisomeric indazolinones 4 and 5 is clear evidence that in case of the indazolinone hinge, both tautomers are equally favored, and should be considered in design of inhibitors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptor 2 de Factores de Crecimiento Endotelial Vascular
/
Inhibidores de Proteínas Quinasas
/
Indazoles
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos