Abstract
A series of 5-substituted 1,2,4-oxadiazoles and 1,2,4-thiadiazoles were prepared as muscarinic acetylcholine receptor agonists and evaluated for their insecticidal activity. These derivatives were synthesized through sequential reactions consisting of the condensation of pyridinecarboamides or pyridinecarbothioamides with N,N-dimethylacetamide dimethyl acetal, cyclization with hydroxylamine, quaternization by alkyl halide and reaction with sodium borohydride. All 1,2,4-oxadiazoles and 1,2,4-thiadiazoles synthesized were evaluated for insecticidal activity and their structure-activity relationships are discussed. It was discovered that many compounds were active against representative insects such as Nilaparvata lugens, Nephotettix cincticeps and Aphis craccivora. In particular, it was also found that 3-pyridyl-substituted derivatives of 1,2,4-oxadiazole and 1,2,4-thiadiazole exhibited good insecticidal activity against all the insects tested. Among the compounds evaluated, 3-methyl-5-(1,2,5,6-tetrahydropyridin-3-yl)-1,2,4-thiadiazole (9m-2) showed the highest activity against Nilaparvata lugens, and provided a high level of activity against the imidacloprid-resistant strain. Based on the preliminary binding assay using the binding inhibition of mAChR antagonist [3H]NMS to the nerve-cord membranes as an index of the binding activity, 9m-2 exhibited a range of potencies for the insect muscarinic receptor.
