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

Feng-Yun Li,Jia-Ning Gong,Gen Li,Jing-Bo Liu

doi:10.3390/molecules24244440

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.

Highlights

By 2050, the global population is projected to grow to over 9 billion, with the associated demand for increasing food production [1,2]
Intermediates 2 were prepared by treated benzoyl chloride derivatives 1 with tert-butylcarbazate [35]
Intermediates 6 were synthesized by treating L-cysteine 5 with benzonitrile derivatives 4 in the presence of sodium bicarbonate and sodium hydroxide in the mixture of methanol and water, according to our previous report with some improvement [25]

Summary

Introduction

By 2050, the global population is projected to grow to over 9 billion, with the associated demand for increasing food production [1,2]. Plant diseases mainly caused by fungi, viruses, oomycetes, and bacteria have caused severe losses to the yield of crops in the world per year. Some efficient measures have been taken to resolve the above problem, and it is well known that the invention and use of agrochemicals play an important role in reducing crop loss caused by plant diseases. Many fungal, virus, oomycete, and bacteria species have developed resistance to some of the currently available agrochemicals due to long-term use of traditional pesticides with a single mode of action [3,4,5,6]. The studies found that a large-scale outburst of drug resistance can be fast accelerated within a relatively short period once resistant populations emerge, which will further increase the difficulty in solving the severe problem and the potential risks on food production [7,8]. Scientists have been dedicated to developing novel agrochemicals with innovative skeletons, novel mechanisms of action, and eco-friendly characteristics

Methods

Results

Conclusion