A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a-o) which are analogues of fluconazole, have been designed and synthesized for the first time by the click reaction on the basis of computational docking experiments to the active site of the cytochrome P450 14α-demethylase (CYP51). Their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. The in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi.