Synthesis, characterization, and biological evaluation of novel diclofenac prodrugs.
J Med Chem
; 54(5): 1202-10, 2011 Mar 10.
Article
en En
| MEDLINE
| ID: mdl-21250699
Diclofenac ester pro drugs (4, 5, 6) were synthesized and evaluated in vitro and in vivo for their potential use for oral delivery, with the aim of obtaining enzymatically labile and less ulceration drugs than the parent drug diclofenac sodium (1a). Prodrugs 4, 5, 6 were found to be potent anti-inflammatory drugs with less ulcerogenic potential than the parent diclofenac sodium. Prodrugs 4, 5, 6 rapidly underwent enzymatic hydrolysis to release the parent drug diclofenac in 30-60 min in rat liver microsomes (RLM) and rat plasma (RP). Prodrugs were found to be more lipophilic when the partition coefficient was measured in 1-octanol and buffer system at pH 7.4 and 3.0. Diclofenac prodrugs 4, 5, 6 were found to be crystalline in nature (analyzed by PXRD). Prodrug 4 was found to be a superior candidate for the treatment of chronic inflammatory diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Profármacos
/
Antiinflamatorios no Esteroideos
/
Diclofenaco
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Estados Unidos