Metabolism of Flufenpyr-ethyl in Rats and Mice

Abstract

The metabolism of flufenpyr-ethyl [ethyl 2-chloro-5-[1,6-dihydro-5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1-yl]-4-fluorophenoxyacetate] was examined in rats and mice. [Phenyl-(14)C]flufenpyr-ethyl was administered to rats and mice as a single oral dose at a level of 500 mg/kg, and (14)C-excretion was examined. Total (14)C-recoveries within 7 days after administration were 93.2 to 97.5% (feces, 42.0 to 46.0%; and urine, 47.2 to 55.5%) in rats and 92.6 to 96.4% (feces, 26.7 to 32.7%; and urine, 59.9 to 69.7%) in mice. (14)C-Excretion into expired air was not detected in rats (expired air of mice was not analyzed). No marked species- or sex-related differences were observed in the rate of (14)C-elimination, but a relatively higher excretion into the urine of mice was observed compared to that in rats. (14)C-residues in tissue 7 days after administration were relatively high for liver, hair, skin, and kidney, but total (14)C-residues were low, below 0.2% of the dose. An ester cleaved metabolite (S-3153acid) was the major metabolite in feces and urine. Hydroxylation of the methyl group on the C5 of the pyridazine ring and ether cleavage were also observed. No sex-related differences were observed in (14)C-elimination, (14)C-distribution, and metabolite profiles, and metabolism of flufenpyr-ethyl in rats and mice was similar. In vitro metabolism of flufenpyr-ethyl was examined using stomach and intestinal contents and blood and liver S9 fractions (postmitochondrial supernatant fractions) in rats. S-3153acid was detected as a major metabolite in the presence of intestinal contents and blood and liver S9 fractions, and a small amount was also formed in the presence of stomach contents, indicating that the parent compound is rapidly metabolized by intestinal contents and blood and liver S9 fractions through ester cleavage.

Pyridazine Chemistry in Crop Protection

“…Fluthiacet‐methyl ( 8 ) is a so‐called propesticide; its in vivo isomerization by glutathione S‐transferase leading to a corresponding urazole metabolite is entirely responsible for the strong herbicidal activity against annual broadleaf weeds in corn, such as Abutilon theophrasti (velvetleaf) and Chenopodium album (pigweed) . Flufenpyr‐ethyl ( 9 ) controls efficiently A. theophrasti and Ipomoea purpurea (morning glory) in corn, soybean, and sugar cane . The plant growth regulator sintofen ( 10 ) is primarily used as hybridizing agent for the sterilization of spring and winter wheat (Fig.…”

Design, Synthesis, and Biological Evaluation of Pyridazinone-Containing Derivatives As Novel Protoporphyrinogen IX Oxidase Inhibitor

“…7,27 Flufenpyr-ethyl, a commercial PPOinhibiting herbicide developed by Sumitomo Chemical, acts swiftly, showing significant necrosis symptoms within a few hours after application. 28 The aforementioned four herbicides share the common feature of bearing the pyridazinone core moiety, which exhibits bioactive properties, including antiinflammatory, bactericidal, insecticidal, and herbicidal properties. 25 Those examples indicate that pyridazinone is a promising moiety for the discovery of novel herbicides.…”

“…Chloridazon serves as an inhibitor and selective herbicide of plant photosynthesis photoreceptor II (PSII) . Dioxopyritrione, a new selective herbicide discovered by Syngenta, targets 4-hydroxyphenylpyruvate dioxygenase (HPPD) in the plastoquinone (PQ) biosynthesis pathway. , Flufenpyr-ethyl, a commercial PPO-inhibiting herbicide developed by Sumitomo Chemical, acts swiftly, showing significant necrosis symptoms within a few hours after application . The aforementioned four herbicides share the common feature of bearing the pyridazinone core moiety, which exhibits bioactive properties, including anti-inflammatory, bactericidal, insecticidal, and herbicidal properties .…”