Novel N‐(1H‐Pyrazol‐5‐yl)nicotinamide Derivatives: Design, Synthesis and Antifungal Activity

Abstract

To discover more effective antifungal agents, twenty N‐(1H‐pyrazol‐5‐yl)nicotinamide derivatives were designed, synthesized, and structurally confirmed by 1H‐NMR, 13C‐NMR, and ESI‐MS. All target compounds were evaluated for their antifungal activities by mycelia growth inhibition. Preliminary screening results displayed that many of these compounds had good fungicidal activity to S. sclerotiorum and V. mali. Compound B4 exhibited antifungal activity against S. sclerotiorum and V. mali with EC50 values of 10.35 and 17.01 mg/L, respectively. The experiment in vivo identified that compound B4 was effective for suppressing rape sclerotinia rot caused by S. sclerotiorum at 50 mg/L. The molecular docking study and scanning electron microscopy preliminary clarified the possible antifungal mechanism of compound B4.

Discovery, Optimization, and Biological Evaluation of Novel Pyrazol-5-yl-phenoxybenzamide Derivatives as Potent Succinate Dehydrogenase Inhibitors

“…According to literature methods, the syntheses of intermediates 3 , 4 , 5 , 6 , and 7 were achieved by utilizing acetonitrile and a substituted ethyl acetate as starting materials. − …”

“…Recently, our research team synthesized a variety of pyrazol-5-yl-benzamide derivatives as potential SDHIs through scaffold hopping and reversing the directionality of amide groups of pyrazole-4-carboxamides (Figure ). − In this work, pyrazol-5-yl-benzamide derivatives were used as lead compounds, and a novel series of pyrazol-5-yl-phenoxybenzamide derivatives were designed and synthesized by replacing the phenyl ring with a diphenyl ether pharmacophore, aiming to identify more potent SDHIs. The target compounds were evaluated for their in vitro fungicidal activities against six common plant pathogenic fungi/oomycete species, followed by an analysis of the resulting structure–activity relationships.…”

Design, Synthesis and Structure-Activity Relationship Studies of Nicotinamide Derivatives as Potent Antifungal Agents by Disrupting Cell Wall

“…In 2019, our team reported that nicotinamide (4, Vitamin B3) showed moderate antifungal activity against C. albicans, including fluconazole-resistant isolates [10]. More recently, Wang and his co-workers also reported several nicotinamide derivatives (6) exhibiting good fungicidal activities after modification of the boscalid structure [11].…”

“…As an important class of heterocyclic derivatives, nicotinamide analogues play an important role in the development of antifungals [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Despite the development and commercialization of several nicotinamide analogues, most have been studied as pesticides ( Figure 1 ).…”

Discovery of Pyrazole-5-yl-amide Derivatives Containing Cinnamamide Structural Fragments as Potential Succinate Dehydrogenase Inhibitors

“…Cinnamamide is a key functional group, working synergistically with the morpholine backbone to ultimately screen out the active molecules. In addition, nicotinamide derivatives exhibit a wide range of pharmacological activity and have been used to develop novel drugs. , For example, the nicotinamide skeleton has been widely used as a versatile pharmacophore in agrochemicals, including boscalid (fungicide), diflufenican (herbicide), and flonicamid (insecticide) (Figure B). These findings suggested the potential of cinnamamide and nicotinamide derivatives as novel fungicides against agricultural pathogens.…”