Design, synthesis and in vitro/in vivo evaluation of orally bioavailable prodrugs of a catechol-O-methyltransferase inhibitor.
Bioorg Med Chem Lett
; 20(8): 2614-6, 2010 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-20231095
ABSTRACT
Compound 1 is an investigational, nanomolar inhibitor of catechol-O-methyltransferase (COMT) that suffers from poor oral bioavailability, most probably due to its low lipophilicity throughout most of the gastrointestinal tract and, to a lesser extent, its rapid systemic clearance. Several lipophilic esters were designed as prodrugs and synthesized in an attempt to optimize presystemic drug absorption. A modest twofold increase in 6-h exposure of 1 was observed with two prodrugs, compared to that of 1, after oral treatment in rats.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pró-Fármacos
/
Inibidores Enzimáticos
/
Inibidores de Catecol O-Metiltransferase
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article