Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists.
Bioorg Med Chem
; 14(8): 2725-46, 2006 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-16377201
ABSTRACT
A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Piperidinas
/
Prolina
/
Integrina alfa4beta1
/
Acetatos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón