The discovery of fluoropyridine-based inhibitors of the factor VIIa/TF complex--Part 2.
Bioorg Med Chem Lett
; 16(4): 1060-4, 2006 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-16289811
ABSTRACT
The activated factor VII/tissue factor complex (FVIIa/TF) is known to play a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. A fluoropyridine-based series of FVIIa/TF inhibitors was discovered which utilized a diisopropylamino group for binding in the S2 and S3 binding pockets of the active site of the enzyme complex. In this series, an enhancement in binding affinity was observed by substitution at the 5-position of the hydroxybenzoic acid sidechain. An X-ray crystal structure indicates that amides at this position may increase inhibitor binding affinity through interactions with the S1'/S2' pocket.
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Tromboplastina
/
Fator VIIa
/
Inibidores Enzimáticos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article