A series of 4-substituted 5-(4-piperidyl)-3-isothiazolols has been synthesized to study their antagonism of small brown planthopper, common cutworm, and housefly GABA receptors. The 4-unsubstituted compound showed weak antagonism of these insect GABA receptors. Pharmacological assays indicated that the introduction of bicyclic aromatic substituents into the 4-position of the 3-isothiazolol ring markedly enhances the antagonist activity of the 3-isothiazolol analogues. The 2-naphthyl and the 3-biphenyl analogues displayed high antagonist potencies in the low micromolar range (IC50 = 20-30 �M) against housefly GABA receptors; the 2-naphthyl analogue caused a parallel, rightward shift of the GABA concentration-response curve, suggesting competitive antagonism by these compounds. The potencies of the 2-naphthyl and the 3-biphenyl analogues are considerably higher than those of compounds previously reported as competitive antagonists in insect GABA receptors.

4-Aryl-5-(4-piperidyl)-3-isothiazolols act as novel competitive antagonists for insect GABA receptors

248th National Meeting (2014)

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