Design, Synthesis, and Antifungal Activities of Novel 1H-Triazole Derivatives Based on the Structure of the Active Site of Fungal Lanosterol 14α-Demethylase (CYP51)

A series of fluconazole (1) analogues, compounds 3a–k, were prepared as potential antifungal agents. They were designed by computational docking experiments to the active site of the cytochrome P450 14α‐sterol demethylase (CYP51), whose crystal structure is known. Preliminary biological tests showed that most of the target compounds exhibit significant activities against the eight most‐common pathogenic fungi. Thereby, the most potent congener, 1‐[(4‐tert‐butylbenzyl)(cyclopropyl)amino]‐2‐(2,4‐difluorophenyl)‐3‐(1H‐1,2,4‐triazol‐1‐yl)propan‐2‐ol (3j), was found to exhibit a broad antifungal spectrum, being more active against Candida albicans, Candida tropicalis, Cryptococcus neoformans, Microsporum canis, and Trichophyton rubrum (MIC80