Identification of urine metabolites of TFAP, a cyclooxygenase-1 inhibitor

Hiroki Kakuta, Ryosuke Fukai, Zheng Xiaoxia, Fuminori Ohsawa, Takeshi Bamba, Kazumasa Hirata, Akihiro Tai

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Only a few COX-1-selective inhibitors are currently available, and the research on COX-1 selective inhibitors is not fully developed. The authors have produced several COX-1 selective inhibitors including N-(5-amino-2-pyridinyl)-4-trifluoromethylbenzamide: TFAP (3). Although 3 shows potent analgesic effect without gastric damage, the urine after administration of 3 becomes red-purple. Since the colored-urine should be avoided for clinical use, in this research we examined the cause of the colored-urine. UV-vis spectra and LC-MS/MS analyses of urine samples and metabolite candidates of 3 were performed to afford information that the main reason of the colored urine is a diaminopyridine (4), produced by metabolization of 3. This information is useful to design new COX-1 selective inhibitors without colored urine based on the chemical structure of 3.

Original languageEnglish
Pages (from-to)1840-1843
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number6
DOIs
Publication statusPublished - Mar 15 2010
Externally publishedYes

Fingerprint

Cyclooxygenase 1
Cyclooxygenase Inhibitors
Metabolites
Urine
Analgesics
Research
Stomach
N-(5-amino-2-pyridinyl)-4-trifluoromethylbenzamide

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Identification of urine metabolites of TFAP, a cyclooxygenase-1 inhibitor. / Kakuta, Hiroki; Fukai, Ryosuke; Xiaoxia, Zheng; Ohsawa, Fuminori; Bamba, Takeshi; Hirata, Kazumasa; Tai, Akihiro.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 6, 15.03.2010, p. 1840-1843.

Research output: Contribution to journalArticle

Kakuta, Hiroki ; Fukai, Ryosuke ; Xiaoxia, Zheng ; Ohsawa, Fuminori ; Bamba, Takeshi ; Hirata, Kazumasa ; Tai, Akihiro. / Identification of urine metabolites of TFAP, a cyclooxygenase-1 inhibitor. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 6. pp. 1840-1843.
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