Design, Synthesis, and Evaluation of the Antifungal Activity of Novel Pyrazole–Thiazole Carboxamides as Succinate Dehydrogenase Inhibitors

Succinate dehydrogenase (SDH) is regarded as a promising target for fungicide discovery. To continue our ongoing studies on the discovery of novel SDH inhibitors as fungicides, novel pyrazole-thiazole carboxamides were designed, synthesized, and evaluated for their antifungal activity. The results indicated that compounds 9ac, 9bf and 9cb showed excellent in vitro activities against Rhizoctonia cerealis with EC50 values from 1.09 to 4.95 mg/L, superior to the commercial fungicide thifluzamide (EC50 = 23.09 mg/L). Compound 9cd (EC50 = 0.72 mg/L) was far more active than thifluzamide (EC50 = 4.88 mg/L) against Sclerotinia sclerotiorum. Compound 9ac exhibited promising in vivo activity against Rhizoctonia solani (90% at 10 mg/L), which was better than thifluzamide (80% at 10 mg/L). The field experiment showed that compound 9ac had 74.40% efficacy against R. solani at the 15th day after 2 consecutive sprayings at an application rate of 4.8 g ai/667 m2, which was close to thifluzamide (83.27%). Furthermore，molecular docking explained the possible binding mode of compound 9ac in the RcSDH active site. Our studies indicated that pyrazole-thiazole-carboxamide hybrid is a new scaffold of SDH inhibitors.