Synthesis and evaluation of novel 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols as antifungal agents.
A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure-activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS, (1)H NMR and (13)C NMR. Results of preliminary antifungal tests against six human pathogenic fungi (Candida albicans, Candida parapsilosis, Cryptococcus neoformans, Candida tropicalis, inherently fluconazole-resistant Candida krusei, Candida glabrata) in vitro showed that all title compounds exhibited activity against fungi tested to some extent except against C. tropicalis. Compound 5b showed higher activity against C. albicans, C. parapsilosis and C. krusei than fluconazole, and its MIC values were determined to be 0.5microg/mL, 1microg/mL and 4microg/mL, respectively. Compound 5k showed higher activities against Torulopsis glabrata than fluconazole (with the MIC value of 2microg/mL). Compounds 5a, 5c, 5f, 5g, 5i exhibited higher activities against C. parapsilosis than fluconazole (with the MIC values of 2microg/mL, 2microg/mL, 2microg/mL, 1microg/mL and 2microg/mL, respectively).
Sun
Qing-Yan
QY
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Guohe Road 325, Shanghai 200433, People's Republic of China.
Zhang
Wan-Nian
WN
Xu
Jian-Ming
JM
Cao
Yong-Bing
YB
Wu
Qiu-Ye
QY
Zhang
Da-Zhi
DZ
Liu
Chao-Mei
CM
Yu
Shi-Chong
SC
Jiang
Yuan-Ying
YY
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001393:Azoles; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D020005:Propanols; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001393:Azoles; D010879:Piperazines; D020005:Propanols