1.
Bioorg Med Chem
; 14(13): 4379-92, 2006 Jul 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-16529937
RESUMEN
Herein, we report on the identification of three potent glycine and related amino acid-based series of FXa inhibitors containing a neutral P1 chlorophenyl pharmacophore. A X-ray crystal structure has shown that constrained glycine derivatives with optimized N-substitution can greatly increase hydrophobic interactions in the FXa active site. Also, the substitution of a pyridone ring for a phenylsulfone ring in the P4 sidechain resulted in an inhibitor with enhanced oral bioavailability.