Identification of glutathione-derived metabolites from an IP receptor antagonist.
Drug Metab Dispos
; 32(12): 1482-90, 2004 Dec.
Article
em En
| MEDLINE
| ID: mdl-15371298
ABSTRACT
The metabolic fate of three aromatic carboxylic acid analogs under evaluation as prostaglandin I2-preferring receptor antagonists was studied. The initial analog with unsubstituted phenyl groups was subject to a complex set of aromatic oxidative biotransformations. By introduction of one or two fluorines, these pathways were inhibited. All three analogs were metabolized to a wide variety of carboxylic acid conjugates. Among these were several conjugates formed via secondary metabolism and oxidation of acyl glutathione intermediates. Two of the structure classes, represented by the S-methyl-N-cysteinylglycine conjugate and the N-cysteinylglycine disulfide conjugates, have been described only rarely in the literature. The related S-oxide of the S-methyl-N-cysteinylglycine conjugate and the N,S-bis-acyl derivative of cysteinylglycine are here described for the first time as conjugate metabolites of carboxylic drugs.
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Base de dados:
MEDLINE
Assunto principal:
Epoprostenol
/
Receptores de Epoprostenol
/
Glutationa
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article