1122022-02-9Relevant articles and documents
The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels
Ozoe, Yoshihisa,Asahi, Miho,Ozoe, Fumiyo,Nakahira, Kunimitsu,Mita, Takeshi
, p. 744 - 749 (2010)
A structurally unique isoxazoline class compound, A1443, exhibits antiparasitic activity against cat fleas and dog ticks comparable to that of the commercial ectoparasiticide fipronil. This isoxazoline compound inhibits specific binding of the γ-aminobutyric acid (GABA) receptor channel blocker [3H]4′-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) to housefly-head membranes, with an IC50 value of 455 pM. In contrast, the IC50 value in rat-brain membranes is >10 μM. To study the mode of action of this isoxazoline, we utilized MdGBCl and MdGluCl cDNAs, which encode the subunits of housefly GABA- and glutamate-gated chloride channels, respectively. Two-electrode voltage clamp electrophysiology was used to confirm that A1443 blocks GABA- and glutamate-induced chloride currents in Xenopus oocytes expressing MdGBCl or MdGluCl channels, with IC50 values of 5.32 and 79.9 nM, respectively. Blockade by A1443 was observed in A2′S-MdGBCl and S2′A-MdGluCl mutant channels at levels similar to those of the respective wild-types, and houseflies expressing A2′S-MdGBCl channels were as susceptible to A1443 as standard houseflies. These findings indicate that A1443 is a novel and specific blocker of insect ligand-gated chloride channels.
PROCESS FOR PREPARATION OF OPTICALLY ENRICHED ALDOL COMPOUNDS
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, (2020/05/28)
The present invention relates to a process for preparing benzylic amidesof formula (I) wherein the variables are as defined in the specification, and the shown enantiomer has at least 50 % ee; by condensation of a ketone o formula (II) with an acetyl compound of formula (III) in the presence of a catalystof formula (IV) wherein the variables are as defined in the specification.
Absolute configuration assignment of (+)-fluralaner using vibrational circular dichroism
Kong, John,Joyce, Leo A.,Liu, Jinchu,Jarrell, Tiffany M.,Culberson, J. Chris,Sherer, Edward C.
, p. 854 - 864 (2017/11/20)
The absolute configurations of the separated enantiomers of fluralaner, a racemic animal health product used to prevent fleas and ticks, have been assigned using vibrational circular dichroism (VCD). The crystallographic structure of the active enantiomer (+)-fluralaner has previously been shown to have the (S) configuration using small molecule crystallography. We sought a faster analytical method to determine the absolute configuration of the separated enantiomers. When comparing the measured IR (infrared) and VCD spectra, it is apparent that the amide carbonyl groups appear in the IR but are nearly absent in the VCD. Computational work to calculate the VCD and IR using in vacuo models, implicit solvation, and explicitly solvated complexes has implicated conformational averaging of the carbonyl VCD intensities.
METHOD FOR CATALYTIC ASYMMETRIC SYNTHESIS OF OPTICALLY ACTIVE ISOXAZOLINE COMPOUND, AND OPTICALLY ACTIVE ISOXAZOLINE COMPOUND
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Paragraph 0236; 0237; 0238; 0252, (2014/12/09)
There is provided a method for catalytic asymmetric synthesis of optically active isoxazoline compound and an optically active isoxazoline compound. A method for catalytic asymmetric synthesis of optically active isoxazoline compound of a formula (6) including reacting an α,β-unsaturated carbonyl compound of a formula (1) and a hydroxylamine in a solvent in the presence of a base by adding a chiral phase transfer catalyst. An optically active isoxazoline compound of a formula (13) that can be synthesized by the method.
