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

Author:
Nagahori, H., Yoshino, H., Tomigahara, Y., Isobe, N., Kaneko, H., Nakatsuka, I.
Source:
Journal of agricultural and food chemistry 2000 v.48 no.11 pp. 5754-5759
ISSN:
0021-8561
Subject:
fungicides, metabolism, metabolites, urine, feces, rats, humans, cytochrome P-450
Abstract:
Urinary and fecal metabolites in male rats treated with a 14C-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.
Agid:
1361966