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

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.

journal_name

Bioorg Med Chem Lett

authors

Kakuta H,Fukai R,Xiaoxia Z,Ohsawa F,Bamba T,Hirata K,Tai A

doi

10.1016/j.bmcl.2010.01.161

subject

Has Abstract

pub_date

2010-03-15 00:00:00

pages

1840-3

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)00185-X

journal_volume

20

pub_type

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