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Identification of the major metabolites of 5-n-butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one, a new angiotensin type 1 receptor antagonist, in rat bile by HPLC-diode array detection-MS and HPLC-MS/MS.

Abstract
5-n-Butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one (1b), a new non-peptide angiotensin type 1 receptor antagonist, has been observed to play a positive role in the treatment of hypertension in preclinical tests. Rats were dosed with the drug, and the major metabolites in the bile were separated by gradient elution high-performance liquid chromatography. HPLC-diode array detection-mass spectrometry, HPLC-electrospray ionization MS/MS methods in negative ion mode and collision-induced dissociation were used to elucidate the structures of the major metabolites of 1b. One dihydroxylated 1b (M1), two monohydoxylated 1b (M2, M3) and one 1b monoglucuronide (M5) were found in male rat bile; however, three monohydoxylated 1b (M2, M3, M4) and one 1b monoglucuronide (M5) were found in female rat bile. These metabolites greatly differ in amount between male and female rat bile.
AuthorsBei Yan, Guangji Wang, Jianguo Sun, Xiaoyu Li, Yuanting Zheng, Hua Ai, Hua Lv, Xiaoming Wu, Jinyi Xu
JournalBiomedical chromatography : BMC (Biomed Chromatogr) Vol. 21 Issue 9 Pg. 912-24 (Sep 2007) ISSN: 0269-3879 [Print] England
PMID17428010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright (c) 2007 John Wiley & Sons, Ltd.
Chemical References
  • 5-n-butyl-4-(4-(2-(1H-tetrazol-5-yl)-1H-pyrrol-1-yl)phenylmethyl)-2,4-dihydro-2-(2,6-dichlorophenyl)-3H-1,2,4-triazol-3-one
  • Receptor, Angiotensin, Type 1
  • Tetrazoles
  • Triazoles
Topics
  • Animals
  • Bile (metabolism)
  • Biotransformation
  • Chromatography, High Pressure Liquid (methods)
  • Female
  • Male
  • Rats
  • Receptor, Angiotensin, Type 1 (drug effects)
  • Tandem Mass Spectrometry (methods)
  • Tetrazoles (metabolism, pharmacokinetics)
  • Triazoles (metabolism, pharmacokinetics)

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