Identification of urine metabolites of TFAP, a cyclooxygenase-1 inhibitor
| Autor: | Kazumasa Hirata, Akihiro Tai, Ryosuke Fukai, Zheng Xiaoxia, Takeshi Bamba, Hiroki Kakuta, Fuminori Ohsawa |
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| Rok vydání: | 2010 |
| Předmět: |
Analgesic effect
Metabolite Clinical Biochemistry Aminopyridines Pharmaceutical Science Urine Pharmacology Tandem mass spectrometry Biochemistry chemistry.chemical_compound Tandem Mass Spectrometry Drug Discovery Lc ms ms Cyclooxygenase Inhibitors Molecular Biology biology Chemistry Organic Chemistry Chromatography liquid Fully developed Benzamides Cyclooxygenase 1 biology.protein Molecular Medicine Spectrophotometry Ultraviolet Cyclooxygenase Chromatography Liquid |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:1840-1843 |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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