Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

Abstract

Up to now, a total of 24 succinate dehydrogenase inhibitors (SDHIs) fungicides have been commercialized, and SDHIs fungicides were also one of the most active fungicides developed in recent years. Carboxamide derivatives represented an important class of SDHIs with broad spectrum of antifungal activities. In this review, the development of carboxamide derivatives as SDHIs with great significances were summarized. In addition, the structure−activity relationships (SARs) of antifungal activities of carboxamide derivatives as SDHIs was also summarized based on the analysis of the structures of the commercial SDHIs and lead compounds. Moreover, the cause of resistance of SDHIs and some solutions were also introduced. Finally, the development trend of SDHIs fungicides was prospected. We hope this review will give a guide for the development of novel SDHIs fungicides in the future.

Rational Design, Synthesis, and Biological Evaluation of Fluorine- and Chlorine-Substituted Pyrazol-5-yl-benzamide Derivatives as Potential Succinate Dehydrogenase Inhibitors

“…Over the past few years, a lot of research has been conducted on the optimization of pyrazole-4-carboxamides, and various effective strategies have been developed, including replacing amides with urea, thiourea, or hydrazides; , introducing suitable N substituents like aryl/biphenyl groups, , diphenyl ether, or diarylamine scaffolds to the amide moiety of pyrazole-4-carboxamides as a hydrophobic tail; and modifying pyrazole-4-carboxamides with pyrazole rings substituted by various groups at different positions . As shown in Figure B, some SDHIs were also optimized by introducing a fluorine or chlorine atom into the amine part of pyrazole-4-carboxamides.…”

Design, Synthesis, and Biological Evaluation of Novel Pyrazol-5-yl-benzamide Derivatives Containing Oxazole Group as Potential Succinate Dehydrogenase Inhibitors

“…18 According to the investigation, as many as half of 24 commercialized SDH inhibitors contain pyrazole-4carboxamides skeleton. 19 Over the past few years, many research groups have optimized the pyrazole-4-carboxamides scaffold, such as the modification of the pyrazole ring, introducing a skeleton containing diphenyl ether 20 and diarylamine 21 into that amine part, replacing amides with urea/thiourea, 22 hydrazides, 23 and oxime ethers , 24 and hopping and inversing the amide groups. 25 Consequently, the structural modification and optimization of the pyrazole-4-carboxamides scaffold may provide another important direction for the development of SDH inhibitors.…”

Novel Pyrazole Carboxamide Containing a Diarylamine Scaffold Potentially Targeting Fungal Succinate Dehydrogenase: Antifungal Activity and Mechanism of Action

“…Succinate dehydrogenase (SDH) called as a mitochondrial complex II played an important role in the Krebs cycle and electron transport of mitochondria. − Inhibition of the SDH would disturb the Krebs cycle and result in the death of pathogens, so it was proved that the SDH was an ideal target for the development of novel fungicides. − Till now, because 24 kinds of commercial SDH inhibitors (SDHIs) had a unique mechanism of action, changeable structures, and good antifungal activities, they have been applied as a category of agricultural fungicides. , However, because usages of SDHIs were not restricted and their effective alternatives were scarce, such as resistance to commercially available pyrazole carboxamides (Figure ), many fungi have developed various resistances. − …”

“…6−9 Till now, because 24 kinds of commercial SDH inhibitors (SDHIs) had a unique mechanism of action, changeable structures, and good antifungal activities, they have been applied as a category of agricultural fungicides. 10,11 However, because usages of SDHIs were not restricted and their effective alternatives were scarce, such as resistance to commercially available pyrazole carboxamides (Figure 1), many fungi have developed various resistances. 12−16 In recent years, to develop novel SDHIs, we reported a series of novel pyrazole carboxamides containing a diarylamine scaffold (Figure 1) that had good antifungal activities, especially against Rhizoctonia solani.…”