Discovery of potent orally active thrombin receptor (protease activated receptor 1) antagonists as novel antithrombotic agents.
J Med Chem
; 48(19): 5884-7, 2005 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-16161991
ABSTRACT
Structurally novel thrombin receptor (protease activated receptor 1, PAR-1) antagonists based on the natural product himbacine are described. The prototypical PAR-1 antagonist 55 showed a Ki of 2.7 nM in the binding assay, making it the most potent PAR-1 antagonist reported. 55 was highly active in several functional assays, showed excellent oral bioavailability in rat and monkey models, and showed complete inhibition of agonist-induced ex vivo platelet aggregation in cynomolgus monkeys after oral administration.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Piridinas
/
Receptor PAR-1
/
Alcaloides
/
Fibrinolíticos
/
Furanos
/
Compostos Heterocíclicos com 3 Anéis
/
Naftalenos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos