The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels

Uso do fluralaner no tratamento da demodicidose canina juvenil generalizada: relato de caso

“…O fluralaner pertence a um grupo de ectoparasiticidas, denominados isoxazolinas, e apresenta atividade contra o ácido γ-aminobutírico e os canais de cloro, ativados por glutamato e com seletividade significativamente maior pelos neurônios dos artrópodes em detrimento dos neurônios dos hospedeiros mamíferos (Ozoe et al, 2010). Esse fármaco tem ação inseticida, a qual combate pulgas e carrapatos, além de ação acaricida descoberta recentemente (Fourie et al, 2015).…”

Enantioselective Synthesis of Trifluoromethyl‐Substituted 2‐Isoxazolines: Asymmetric Hydroxylamine/Enone Cascade Reaction

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Heterocycles containing a trifluoromethyl group are representatives of a major structure type in agricultural and medicinal chemistry, and thus the development of a simple and flexible method to generate a novel trifluoromethylated heterocyclic system has received much attention.[1] Trifluoromethyl-substituted 2-isoxazolines are amongst an important class of heterocyclic compounds with remarkable biological activities, and they make interesting synthetic targets.[2] Since the first discovery of the structurally unique 3,5-diaryl-5-(trifluoromethyl)-2-isoxazoline derivatives 1 (Figure 1) as pest control agents in 2004, [3a] the search for new agrochemicals and veterinary medicines has focused largely on this skeleton, [3] despite their diverse structural variants.[2] Thus far, more than 20 000 compounds have been synthesized and patented in the past 5 years (the results of substructure searching using 1 with Scifinder), and many promising drug candidates have been disclosed including an antiparasiticide compound of either type A or B (Figure 1).

[3] More interestingly, recent biological evaluation of the optically active type B compound (X 6 = CONHCH 2 COCH 2 CF 3 ), obtained by HPLC methods using a chiral stationary phase, revealed that the R enantiomer of B is inactive and the S enantiomer is the active component.

[3b] Once the importance of the optical purity of these compounds was verified, the next challenge was to control the stereochemistry at a quaternary carbon center bearing a CF 3 group.

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Mosquitocidal activity and mode of action of the isoxazoline fluralaner

“…Currently commercialized as a parasiticide, fluralaner was reported to be safe to dogs at or above recommended treatments [25,26]. In radioligand binding studies on rat brain membranes, 10 µM of fluralaner showed around 40% inhibition of radiolabeled 4-ethynyl-4-N-propylbicycloorthobenzoate (EBOB) binding, which is more than 2000-fold less sensitive than its binding to housefly GABA receptors [10,12]. Additionally, fluralaner had low activities on either recombinant β 3 homopentamers or α 1 β 2 γ 2 heteropentamers [10,12].…”

“…In radioligand binding studies on rat brain membranes, 10 µM of fluralaner showed around 40% inhibition of radiolabeled 4-ethynyl-4-N-propylbicycloorthobenzoate (EBOB) binding, which is more than 2000-fold less sensitive than its binding to housefly GABA receptors [10,12]. Additionally, fluralaner had low activities on either recombinant β 3 homopentamers or α 1 β 2 γ 2 heteropentamers [10,12]. In the present study, mammalian GABA A α 1 β 3 γ 2 receptors were tested against fluralaner and fipronil.…”