[Synthesis and antifungal activity of novel triazole antifungal agents].
OBJECTIVE
A series of triazole antifungal agents were synthesized to search for novel triazole antifungal agents with more potent activity, less toxicity and broader spectrum.


METHODS
Twenty-one 1-(1H-1, 2, 4-triazolyl)-2-(2, 4-diflurophenyl)-3-(4-substituted-1-piperazinyl)-2-propanols were synthesized, on the basis of the three dimensional structure of P450 cytochrome 14alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.


RESULTS
Results of preliminary biological tests showed that most of title compounds exhibited activity against the eight common pathogenic fungi to some extent and the activities against deep fungi were higher than that against shallow fungi. In general, phenyl and pyridinyl analogues showed higher antifungal activity than that of the phenylacyl analogues.


CONCLUSIONS
Several title compounds showed higher antifungal activities than fluconazole and terbinafine. Compound VIII-1, 4, 5 and IX-3 showed the best antifungal activity with broad antifungal spectrum and were chosen for further study.
Sheng
Chun-quan
CQ
Department of Medicinal Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
Zhu
Jie
J
Zhang
Wan-nian
WN
Song
Yun-long
YL
Zhang
Min
M
Ji
Hai-tao
HT
Yu
Jian-xin
JX
Yao
Jian-zhong
JZ
Yang
Song
S
Miao
Zhen-yuan
ZY
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects; D015725:Fluconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009281:Naphthalenes / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000077291:Terbinafine; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000935:Antifungal Agents; D009281:Naphthalenes; D014230:Triazoles; D015725:Fluconazole; D000077291:Terbinafine