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

作者：Sheng Chunquan; Che Xiaoying; Wang Wenya; Wang Shengzheng; Cao Yongbing; Miao Zhenyuan; Yao Jianzhong^*; Zhang Wannian

来源：European Journal of Medicinal Chemistry, 2011, 46(11): 5276-5282.

DOI：10.1016/j.ejmech.2011.03.019

• Structure-based bioisosterism
• Triazolone
• Azole
• Antifungal

The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. 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. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations.

• 出版日期2011-11
• 单位中国人民解放军第二军医大学