RT Journal Article
SR Electronic
T1 IDENTIFICATION OF GLUTATHIONE-DERIVED METABOLITES FROM AN IP RECEPTOR ANTAGONIST
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1482
OP 1490
DO 10.1124/dmd.104.000471
VO 32
IS 12
A1 William L. Fitch
A1 Pamela W. Berry
A1 Yaping Tu
A1 Ali Tabatabaei
A1 Lee Lowrie
A1 Francisco Lopez-Tapia
A1 Yanzhou Liu
A1 Dov Nitzan
A1 Mohammad R. Masjedizadeh
A1 Aravamuthan Varadarajan
YR 2004
UL http://dmd.aspetjournals.org/content/32/12/1482.abstract
AB 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 car boxylic drugs. The American Society for Pharmacology and Experimental Therapeutics