1. Academic Validation
  2. Metabolism of furametpyr. 1. Identification of metabolites and in vitro biotransformation in rats and humans

Metabolism of furametpyr. 1. Identification of metabolites and in vitro biotransformation in rats and humans

  • J Agric Food Chem. 2000 Nov;48(11):5754-9. doi: 10.1021/jf0001334.
H Nagahori 1 H Yoshino Y Tomigahara N Isobe H Kaneko I Nakatsuka
Affiliations

Affiliation

  • 1 Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 1-98, 3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-0022, Japan. nagahori@sc.sumitomo-chem.co.jp
Abstract

Urinary and fecal metabolites in male rats treated with a (14)C-labeled fungicide, furametpyr [N-(1,3-dihydro-1,1, 3-trimethylisobenzofuran-4-yl)-5-chloro-1, 3-dimethylpyrazole-4-carboxamide, Limber], were purified by a combination of chromatographic techniques, and chemical structures of 14 metabolites were identified by spectroanalyses (NMR and MS). The major biotransformation reactions of furametpyr in rats were found to be (1) N-demethylation, (2) oxidation of the methyl group at C3 of the pyrazole ring, (3) oxidation of the methyl group at C1 of the 1,3-dihydroisobenzofuran ring, (4) hydroxylation at C3 of the 1,3-dihydroisobenzofuran ring, and (5) hydroxylation at C7 of the 1, 3-dihydroisobenzofuran ring. In vitro metabolism by recombinant human Cytochrome P450 revealed that a major biotransformation in humans is N-demethylation, catalyzed by CYP1A1, 1A2, 2C19, and 3A4.

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