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Published on: June 23, 2019
Design, synthesis and structure-activity relationships of new triazole derivatives containing N-substituted
Shengzheng Wang1, Gang Jin, Wenya Wang
1Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
Abstract:
The incidence of invasive fungal infections and resistance to antifungal agents is increasing dramatically. It is highly desirable to develop novel azoles with improved biological profiles. The structure-activity relationship (SAR) of the N-substitutions was investigated in this study. In vitro antifungal activities revealed that sterically large groups were not favored for the N-substitutions. The removal of the N-substitutions had little effect on the antifungal activity. Two compounds with free amine group (i.e.9a and 10a) showed excellent activity with broad antifungal spectrum. The SAR results were supported by molecular docking and the N-substitutions were found to be important for the conformation of the side chains. The SAR and binding mode of the azoles are useful for further lead optimization.
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