DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on September 15, 2004; DOI: 10.1124/dmd.104.000471

0090-9556/04/3212-1482-1490$20.00
DMD 32:1482-1490, 2004

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.104.000471v1
32/12/1482    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fitch, W. L.
Right arrow Articles by Varadarajan, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fitch, W. L.
Right arrow Articles by Varadarajan, A.

IDENTIFICATION OF GLUTATHIONE-DERIVED METABOLITES FROM AN IP RECEPTOR ANTAGONIST

William L. Fitch, Pamela W. Berry, Yaping Tu, Ali Tabatabaei, Lee Lowrie, Francisco Lopez-Tapia, Yanzhou Liu, Dov Nitzan, Mohammad R. Masjedizadeh, and Aravamuthan Varadarajan1

Drug Metabolism and Pharmacokinetics (W.L.F., P.W.B., Y.T., A.T.), Medicinal Chemistry (L.L., F.L.-T., Y.L., D.N.), and Radiochemistry (M.R.M., A.V.) Departments, Roche Palo Alto, LLC, Palo Alto, California

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.

Address correspondence to: William L. Fitch, DMPK Department, Roche Palo Alto, LLC, 3431 Hillview Ave., Palo Alto, CA 94304. E-mail: Bill.fitch{at}roche.com






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2004 by the American Society for Pharmacology and Experimental Therapeutics.