Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Farabi Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Eur J Med Chem. 2022 Mar 5;231:114161. doi: 10.1016/j.ejmech.2022.114161. Epub 2022 Jan 29.
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 voriconazole. 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.
伏立康唑（VCZ）是首个获得批准的具有 1-（1H-1,2,4-三唑-1-基）-2-丁醇取代基的三唑类抗真菌药物。该药物显示出广谱的活性，特别是对酵母和霉菌，为新型全身抗真菌药物开辟了新途径。在 VCZ 侧链的 2-氟嘧啶的修饰导致了包括依氟康唑、阿巴康唑、拉夫康唑和伊曲康唑在内的新一代三唑基丁醇的出现，具有有利的抗真菌谱、增强的药代动力学特性和可耐受的毒性特征。由于三唑基丁醇在新型抗真菌药物的发现和开发中的重要性，在本综述中，我们重点介绍了源于伏立康唑的三唑基丁醇的合成方法和结构多样性。本综述为药物化学家在设计、合成和开发具有更好活性、药代动力学特性和毒性特征的新型潜在抗真菌药物方面提供了重要的研究方向。
