Design, Synthesis and Antifungal Activities of Novel Pyrazole Analogues Containing the Aryl Trifluoromethoxy Group

On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF(3) were designed and synthesized. Their chemical structures were characterized by (1)H and (13)C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 μg/mL. Compounds 1t and 1v exhibited higher activity against all the tested fungi, and 1v displayed the highest activity against F. graminearum with an EC(50) value of 0.0530 μM, which was comparable with commercial pyraclostrobin. Structure–activity relationship analysis showed that, with respect to the R(1) substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R(2) substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.