1.
Bioorg Med Chem Lett
; 13(4): 729-32, 2003 Feb 24.
Artículo
en Inglés
| MEDLINE
| ID: mdl-12639568
RESUMEN
The structure-activity relationship of a novel series of substituted piperazinone-based factor Xa inhibitors is described. The most potent compound 34 displays IC(50) of 0.9 nM.
Asunto(s)
Inhibidores del Factor Xa , Piperazinas/síntesis química , Inhibidores de Serina Proteinasa/síntesis química , Anticoagulantes/síntesis química , Anticoagulantes/química , Sitios de Unión , Diseño de Fármacos , Humanos , Concentración 50 Inhibidora , Modelos Moleculares , Conformación Molecular , Piperazinas/química , Piperazinas/farmacología , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/farmacología , Relación Estructura-Actividad , Trombina/antagonistas & inhibidores
2.
Bioorg Med Chem Lett
; 13(4): 723-8, 2003 Feb 24.
Artículo
en Inglés
| MEDLINE
| ID: mdl-12639567
RESUMEN
A series of novel transition state factor Xa inhibitors containing a variety of lactam ring systems as central templates was synthesized in an expedient manner and allowed for a great deal of structural variability. Among them, the piperazinone-based inhibitors were found to be not only active against factor Xa but also selective over thrombin. Optimization of the P4 moiety yielded several potent compounds with IC(50) below 1 nM against factor Xa.