Metabolism of furametpyr. 1. Identification of metabolites and in vitro biotransformation in rats and humans.
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.
Nagahori
H
H
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
Yoshino
H
H
Tomigahara
Y
Y
Isobe
N
N
Kaneko
H
H
Nakatsuka
I
I
D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005659:Fungicides, Industrial / Q000493:pharmacokinetics*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology; D011720:Pyrazoles / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000378:metabolism
D001572:Benzofurans; D002250:Carbon Radioisotopes; D005659:Fungicides, Industrial; D007527:Isoenzymes; D011720:Pyrazoles; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; C417978:furametpyr