Interspecies in vitro metabolism of the phosphodiesterase-4 (PDE4) inhibitor L-454,560.
J Mass Spectrom
; 41(6): 771-80, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16705670
ABSTRACT
L-454,560 is a potent phosphodiesterase 4 (PDE4) inhibitor which was identified as a development candidate for the treatment of asthma and chronic obstructive pulmonary disease (COPD). As part of the discovery of this compound, interspecies in vitro metabolism data was generated using liver microsomes and hepatocytes in order to understand the metabolic fate of the compound. In microsomes, metabolism of the 3-methyl-1,2,4-oxadiazole ring was the predominant pathway observed, including ring cleavage. In rat hepatocytes, hydroxylation of the methyl group on the oxadiazole ring and double-bond isomerization were the most abundant metabolites observed. No major species differences were found in terms of microsomal metabolite profiles. The use of LC with UV and MS detection is highlighted, as well as information from tandem mass spectrometry and NMR.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Microssomos Hepáticos
/
3',5'-AMP Cíclico Fosfodiesterases
/
Hepatócitos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Mass Spectrom
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Canadá