Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism

► By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. ► Several triazolone-containing triazoles (such as 11d, 11j, 11p and 11q) showed higher antifungal activity and broader spectrum than fluconazole. ► Compounds 11c and 11i showed good activity toward azole-resistant clinical isolate.