Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties.
Bioorg Med Chem Lett
; 25(7): 1635-42, 2015 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-25728130
ABSTRACT
Compound 2 was previously identified as a potent inhibitor of factor XIa lacking oral bioavailability. A structure-based approach was used to design analogs of 2 with novel P1 moieties with good selectivity profiles and oral bioavailability. Further optimization of the P1 group led to the identification of a 4-chlorophenyltetrazole P1 analog, which when combined with further modifications to the linker and P2' group provided compound 32 with FXIa Ki=6.7 nM and modest oral exposure in dogs.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Factor XIa
/
Inhibidores Enzimáticos
/
Indazoles
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2015
Tipo del documento:
Article