Synthesis, fungicidal activity, and 3D-QSAR of tetrazole derivatives containing phenyloxadiazole moieties.

In an effort to discover new agents with good fungicidal activities against CDM (cucumber downy mildew), a series of tetrazole derivatives containing phenyloxadiazole moieties were designed and synthesized. The EC50 values for fungicidal activities against CDM were determined. Bioassay results indicated that most synthesized compounds exhibited potential in vivo fungicidal activity against CDM. A CoMFA (comparative molecular field analysis) model based on the bioactivity was developed to identify some primary structural quality for the efficiency. The values of q2 and r2 for the established model were 0.791 and 0.982 respectively, which reliability and predict abilities were verified. Three analogues (q3, q4, q5) were designed and synthesized based on the model. All these compounds exhibited significant fungicidal activity on CDM with the EC50 of 1.43, 1.52, 1.77 mg·L-1. This work could provide a useful instruction for the further structure optimization.

Design, Synthesis, and Structure-Activity Relationship of Economical Triazole Sulfonamide Aryl Derivatives with High Fungicidal Activity.

Plant fungal diseases have caused great decreases in crop quality and yield. As one of the considerable agricultural diseases, cucumber downy mildew (CDM) caused by pseudoperonospora cubensis seriously influences the production of cucumber. Amisulbrom is a commercial agricultural fungicide developed by Nissan Chemical, Ltd., for the control of oomycetes diseases that is highly effective against CDM. However, the synthesis of amisulbrom has a high cost because of the introduction of the bromoindole ring. In addition, the continuous use of amisulbrom might increase the risk of resistance development. Hence, there is an imperative to develop active fungicides with new scaffolds but low cost against CDM. In this study, a series of 1,2,4-triazole-1,3-disulfonamide derivatives were designed, synthesized, and screened. Compound 1j showed a comparable fungicidal activity with amisulbrom, but it was low cost and ecofriendly. It has the potential to be developed as a new fungicide candidate against CDM. Further investigations of structure-activity relationship exhibited the structural requirements of 1,2,4-triazole-1,3-disulfonamide and appropriate modification in N-alkyl benzylamine groups with high fungicidal activity. This research will provide powerful guidance for the design of highly active lead compounds with a novel skeleton and low cost.