(R)-2-Phenyl-4,5-Dihydrothiazole-4-Carboxamide Derivatives Containing a Diacylhydrazine Group: Synthesis, Biological Evaluation, and SARs

Abstract

A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated. The antifungal activity result indicated that most title compounds against Cercospora arachidicola, Alternaria solani, Phytophthora capsici, and Physalospora piricola exhibited apparent antifungal activities at 50 mg/L, and better than chlorothalonil or carbendazim. The EC50 values of (R)-N’-benzoyl-2-(4-chlorophenyl)-4,5-dihydrothiazole-4-carbohydrazide (I-5) against six tested phytopathogenic fungi were comparable to those of chlorothalonil. The CoMSIA model showed that a proper hydrophilic group in the R1 position, as well as a proper hydrophilic and electron-donating group in the R2 position, could improve the antifungal activity against Physalospora piricola, which contributed to the further optimization of the structures. Meanwhile, most title compounds displayed good insecticidal activities, especially compound (R)-N’-(4-nitrobenzoyl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carbohydrazide (III-3). The insecticidal mechanism results indicated that compound III-3 can serve as effective insect Ca2+ level modulators by disrupting the cellular calcium homeostasis in Mythimna separata.