Synthesis, fungicidal activity, and QSAR of a series of 2-dichlorophenyl-3-triazolylpropyl ethers

A series of new alkyl and arylalkyl ethers of 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, related to the fungicide tetraconazole, were synthesized and tested in vitro or in vivo against seven common pathogens in comparison with tetraconazole. In vitro, most of them exhibited a broad spectrum of activity and an efficacy of the same order of magnitude of the standard, but the activity was influenced by the nature of the substituents. A QSAR study showed that lipophilicity is a major positive parameter in affecting the activity; the second relevant parameter is mu, whereas geometrical descriptors indicate that linear and narrow substituents are more suitable than wide ones. In in vivo assays some compounds had good activity on bean rust, either protective or curative. Sterol analysis showed that the mechanism of action is due to inhibition of 14 alpha-demethylase.