The discovery of YM-60828: a potent, selective and orally-bioavailable factor Xa inhibitor.
Bioorg Med Chem
; 10(5): 1509-23, 2002 May.
Article
en En
| MEDLINE
| ID: mdl-11886813
ABSTRACT
Since Factor Xa (FXa) is well known to play a central role in thrombosis and hemostasis, inhibition of FXa is an attractive target for antithrombotic strategies. As a part of our investigation of a non-peptide, orally available FXa inhibitor, we found that a series of N-[(7-amidino-2-naphthyl)methyl]aniline derivatives possessed potent and selective inhibitory activities. Structure--activity relationship (SAR) of the substituent (R(1)) on the central aniline moiety suggested that increasing lipophilicity caused a detrimental effect on anticoagulant activity (prothrombin time assay) in plasma. Several compounds bearing a hydrophilic substituent in R(1) showed not only potent FXa inhibitory activities but also high anticoagulant activities. The best compound in this series was sulfamoylacetic acid derivative (YM-60828) which was a potent, selective and orally bioavailable FXa inhibitor and was chosen for clinical development.
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Banco de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Antitrombina III
/
Inhibidores del Factor Xa
/
Naftalenos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2002
Tipo del documento:
Article