Structure-based drug design of pyrrolidine-1, 2-dicarboxamides as a novel series of orally bioavailable factor Xa inhibitors.
Chem Biol Drug Des
; 69(6): 444-50, 2007 Jun.
Article
en En
| MEDLINE
| ID: mdl-17581239
ABSTRACT
A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor Xa inhibitors using structure-based drug design. This series consisted of a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) = 0.38 nM), which was shown to be efficacious in a canine electrolytic model of thrombosis with minimal bleeding.
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Banco de datos:
MEDLINE
Asunto principal:
Ácido Pirrolidona Carboxílico
/
Química Farmacéutica
/
Antitrombina III
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2007
Tipo del documento:
Article