Synthesis of pyrazole-4-carboxamides as potential fungicide candidates

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.

Section: Carboxamide Derivatives As Sdhismentioning

confidence: 99%

Section: Carboxamide Derivatives As Sdhismentioning

confidence: 99%

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

Luo

Ning

2022

“…This study aimed to use both the fungicidal lead 3-difluoromethyl-pyrazole-4-carboxylic acid and the plant elicitor lead 3-chloro-1-methyl-1 H -pyrazole-5-carboxylic acid (CMPA) as templates by transferring the position of pyrazole ring substituent groups to design and synthesize novel 5-chloro-4-difluoromethyl-pyrazole-3-carboxamide analogues (Figure ). , It is expected that the target molecules could display both antifungal and inducing plant defense response activities to improve their antifungal functions. And specific bioassays were used to verify the expectation of our molecular design.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel Pyrazole Amides as Potent Fungicide Candidates and Evaluation of Their Mode of Action

Sun

Chen

Huo

et al. 2022

Self Cite

A rational molecule design strategy based on scaffold hopping was applied to discover novel leads, and then a series of novel pyrazole amide derivatives were designed, synthesized, characterized, and evaluated for their antifungal activities. Bioassay results indicated that some target compounds such as S3, S12, and S26 showed good in vivo antifungal activities; among them, S26 exhibited commendable in vivo protective activity with an 89% inhibition rate against Botrytis cinerea on cucumber at 100 μg/mL that is comparable to positive controls boscalid, isopyrazam, and fluxapyroxad. Microscopy observations suggested that S26 affects the normal fungal growth. Fluorescence quenching analysis and SDH (succinate dehydrogenase) enzymatic inhibition studies validated that S26 may not be an SDH inhibitor. Based on induction of plant defense responses testing, S26 enhanced the accumulation of RBOH, WRKY6, WRKY30, PR1, and PAL defense-related genes expression and the defense-associated enzyme phenylalanine ammonia lyase (PAL) expression on cucumber. These findings support that S26 not only displayed direct fungicidal activity but also exhibited plant innate immunity stimulation activity, and it could be used as a promising plant defense-related fungicide candidate.

“…Actually, over a dozen agrochemicals containing pyrazoles have been successfully developed for plant pathogen management (Figure ). − …”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Evaluation of Novel 4-Chloropyrazole-Based Pyridines as Potent Fungicide Candidates

Wang

Kou

Huo

et al. 2022

Self Cite

A rational molecular design approach was developed in our laboratory to guide the discovery of novel sterol biosynthesis inhibitors. Based on the application of bioactivities of heterocyclic rings and molecular docking targeting the sterol biosynthesis 14α-demethylase, a series of 4-chloropyrazole-based pyridine derivatives were rationally designed, synthesized, and characterized and their fungicidal activities were also evaluated. Bioassay results showed that 7e, 7f, and 7m exhibited commendable, diverse antifungal actions that are comparable to those of the positive controls imazalil and triadimefon. The active compounds’ mode of action was further studied by microscopy observations, Q-PCR, and enzyme inhibition assay and discovered that target compounds affect fungal sterol biosynthesis via disturbing RcCYP51 enzyme system. These findings support that their fungicidal mode of action still targets the cytochrome P450-dependent 14α-demethylase as the molecular design did at first. The above results strongly suggest that our rational molecular design protocol is not only practical but also efficient.