Discovery of potent, metabolically stable purine CRF-1 antagonists with differentiated binding kinetic profiles.
Bioorg Med Chem Lett
; 21(20): 6108-11, 2011 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-21889333
ABSTRACT
Optimisation of the potency of a bicyclic CRF antagonist whilst retaining metabolic stability is described. A core change and incorporation of metabolically stable lipophilic groups resulted in a further potency gain without increasing metabolic liability. Pharmacological investigation of binding kinetics led to the identification of compound 25, a sub-nanomolar CRF-1 antagonist with slow dissociation kinetics and an encouraging pharmacokinetic profile.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Purinas
/
Hormônio Liberador da Corticotropina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article