Oxygenated analogues of UK-396082 as inhibitors of activated thrombin activatable fibrinolysis inhibitor.
Bioorg Med Chem Lett
; 20(1): 92-6, 2010 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-19954973
ABSTRACT
A suitable inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa) has the potential to be a novel treatment for thrombosis. The TAFIa inhibitor UK-396082 (1) was used as a starting point to seek more potent analogues. With knowledge of encouraging human pharmacokinetics and toleration for the clinical candidate (1), the programme continued to seek structure-activity relationships (SAR) that could positively impact on both potency and half-life, and therefore the projected dose of any future nominated clinical agent. A series of oxygenated analogues based on compound 1 were prepared to evaluate changes in pharmacology, selectivity and pharmacokinetics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Inibidores de Proteases
/
Carboxipeptidase B2
/
Fibrinolíticos
/
Aminoácidos
/
Imidazóis
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido