Development of an oxazolopyridine series of dual thrombin/factor Xa inhibitors via structure-guided lead optimization.
Bioorg Med Chem Lett
; 15(20): 4411-6, 2005 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-16137886
ABSTRACT
Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridinas
/
Antitrombinas
/
Inhibidores del Factor Xa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos