Synthetic approaches and structural diversity of triazolylbutanols derived from voriconazole in the antifungal drug development

Voriconazole (VCZ) was the first approved triazole antifungal drug with 1-(1H-1,2,4-triazol-1-yl)butan-2-ol substructure. This drug showed a broad spectrum of activity, especially against yeasts and molds, and opened a new avenue toward the novel class of systemic antifungal agents. Modification of 2-fluoropyrimidine in the side chain of VCZ resulted in a newer generation of triazolylbutanols including efinaconazole, albaconazole, ravuconazole, and isavuconazole with the favorable antifungal spectrum, enhanced pharmacokinetic properties, and tolerable toxicity profiles. Due to the importance of triazolylbutanols in the discovery and development of new antifungal agents, in this review we have focused on the synthetic approaches and structural diversity of triazolylbutanols derived from vor-iconazole. This comprehensive review provides highlighting scope for medicinal chemists for the design, synthesis and development of novel potential antifungal drugs having better activity, pharmacokinetic property and toxicity profile.(c) 2022 Elsevier Masson SAS. All rights reserved.

Automated summary

This review focuses on the synthetic approaches and structural diversity of triazolylbutanols derived from voriconazole, highlighting their importance in the design, synthesis, and development of novel antifungal drugs.