Identification of urine metabolites of TFAP, a cyclooxygenase-1 inhibitor.
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.
Kakuta
Hiroki
H
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-Ku, Okayama, Japan. kakuta@pharm.okayama-u.ac.jp
Fukai
Ryosuke
R
Xiaoxia
Zheng
Z
Ohsawa
Fuminori
F
Bamba
Takeshi
T
Hirata
Kazumasa
K
Tai
Akihiro
A
D000631:Aminopyridines / Q000652:urine*; D001549:Benzamides / Q000652:urine*; D002853:Chromatography, Liquid; D051545:Cyclooxygenase 1 / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000652:urine*; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
D000631:Aminopyridines; D001549:Benzamides; D016861:Cyclooxygenase Inhibitors; C550711:N-(5-amino-2-pyridinyl)-4-trifluoromethylbenzamide; D051545:Cyclooxygenase 1