Synthesis and biological activity of novel 1,2-disubstituted benzene derivatives as factor Xa inhibitors.
Bioorg Med Chem
; 13(4): 1305-23, 2005 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-15670939
ABSTRACT
Factor Xa (fXa) is a serine protease that plays a pivotal role in the coagulation cascade. High-throughput screening of the Yamanouchi compound library yielded lead compound 1 with the ability to inhibit fXa at micromolar concentrations. To improve its fXa inhibitory activity and its oral anticoagulant activity, the linker between benzamidine and the central benzene ring was modified and a carboxyl group was introduced at the central benzene ring. The resulting compounds 40b (YM-203552), 41a (YM-202054), and 41c (YM-203558) exhibited potent fXa inhibitory activity and oral anticoagulant activity. In particular, YM-203558 exhibited the most potent oral anticoagulant activity, prolonging PT more than 3-fold at 0.5 and 2.0 h. Additionally, these compounds showed a high degree of selectivity for other serine proteases.
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Bases de datos:
MEDLINE
Asunto principal:
Derivados del Benceno
/
Inhibidores de Serina Proteinasa
/
Inhibidores del Factor Xa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Japón