1.
Bioorg Med Chem Lett
; 17(24): 6910-3, 2007 Dec 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-17976987
RESUMO
Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.
Assuntos
Antitrombina III/síntese química , Antitrombina III/farmacologia , Glicina/análogos & derivados , Anticoagulantes/síntese química , Anticoagulantes/química , Anticoagulantes/farmacologia , Antitrombina III/química , Cristalografia por Raios X , Fator Xa/química , Fator Xa/metabolismo , Glicina/síntese química , Glicina/química , Glicina/farmacologia , Humanos , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
2.
Bioorg Med Chem Lett
; 17(17): 4832-6, 2007 Sep 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-17624775
RESUMO
SAR about the B-ring of a series of N(2)-aroyl anthranilamide factor Xa (fXa) inhibitors is described. B-ring o-aminoalkylether and B-ring p-amine probes of the S1' and S4 sites, respectively, afforded picomolar fXa inhibitors that performed well in in vitro anticoagulation assays.