Design and Discovery of Novel Chiral Antifungal Amides with 2-(2-Oxazolinyl)aniline as a Promising Pharmacophore

Abstract

Inspired by established succinate dehydrogenase inhibitors (SDHIs), our continuing efforts toward the discovery of chiral antifungal amides turned to the optimization of their polar regions with 2-(2-oxazolinyl)aniline as a known pharmacophore. Scaffold hopping and bioactivity-guided convergent synthesis enabled the identification of promising antifungal categories. Fine tuning of the substituents and chirality furnished seven amides (1s, 1t, 2d, 2h, 2j, 3k, and 2l) as antifungal candidates, with EC values lower than 5 mg/L. The first investigation of chiral amides of acyclic acids as SDHIs was conducted, and compound 2d was selected as a promising candidate against Botrytis cinerea, with a preventative efficacy of up to 93.9% at 50 mg/L, which is better than that of boscalid. The different binding models between compounds with different configurations were simulated for compound 2d and its diastereoisomers. The benefits of synthetic accessibility and cost-effectiveness highlight the practical potential for compound 2d as a good alternative to known SDHI fungicides.

Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide

“…1). 15,16 At present, five commercial SDHI fungicides have been successfully developed by structural modification of the amide bridge, including isofetamid, 17 fluopyram, 18 pydiflumetofen, 19 isoflucypram 20 and pyrapropoyne. 21 Fluopyram (Fig.…”

Synthesis, Antifungal Activity, DFT Study and Molecular Dynamics Simulation of Novel 4‐(1,2,4‐Oxadiazol‐3‐yl)‐N‐(4‐phenoxyphenyl)benzamide Derivatives

“…The in vitro fungal inhibition of compounds 3a – j were evaluated at 20 mg/L by the mycelia growth inhibition method, referencing to method previously reported [36] . The specific method can refer to the Supporting Information .…”

Facile and divergent optimization of chromazonarol enabled the identification of simplified drimane meroterpenoids as novel pharmaceutical leads

“…With the continuing interests in the discovery of new antifungal agrochemicals, our basic research was inspired by not only the classical amide fungicides [16][17][18], but also the structurally different drimane hydroquinones and drug-like analogues [19][20][21][22]. Recently, we showcased the potential of (+)-chromazonarol as a novel antifungal scaffold [22], which is unique in agrochemical industry from the standpoint of structural analysis.…”