| Abstract
| - In vitro studies have demonstrated thatN-(4-chloro-3-methyl-5-isothiazolyl)-N-methyl-2-[p-[(α,α,α-trifluoro-p-tolyl)oxy]phenyl]acetamide(2a) undergoes NADPH-dependent metabolism, whichiscatalyzed by monooxygenase enzymes, in rat liver microsomes. Theprimary metabolite in rat wasfound to arise from ring-methyl hydroxylation, whileN-demethylation to giveN-(4-chloro-3-methyl-5-isothiazolyl)-2-[p-[(α,α,α-trifluoro-p-tolyl)oxy]phenyl]acetamide(1) was also observed to occur, butat a slower rate. In microsomal proteins prepared from tobaccobudworm midgut tissues, the reversewas observed, as 1 is the predominant metabolite, whilering-methyl hydroxylation occurs at a slowerrate. The overall rate of metabolism in trout liver microsomes wasfound to be ≈50-fold slowerthan in rat and afforded 1 as the predominant metabolite.Metabolism studies conducted on theN-alkyl-N-(5-isothiazolyl)- andN-(alkyl-isothiazolin-5-ylidene)phenylacetamides(2 and 3) haveshown that the ring-alkylated isomers 3 were converted to1 more rapidly than isomers 2 in allthree species. In general, the rate of conversion to 1,or bioactivation, increased with increasingradical or carbocation stability of the alkyl group in rat and troutliver. In tobacco budworm, however,bioactivation was highest in the ethyl and n-propylanalogues. The ratio of bioactivation in tobaccobudworm to that in trout, used as a predictor of selectivity, wasobserved to be highest with themethyl group. Keywords: Isothiazolylphenylacetamide; isothiazolinylidenephenylacetamide;metabolism; proinsecticide
|
