Design, synthesis and antifungal evaluation of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one

被引：22

作者：

Jiang, Yongwei ^{[1
]}

Cao, Yongbin ^{[2
]}

Zhang, Jun ^{[3
]}

Zou, Yan ^{[1
]}

Chai, Xiaoyun ^{[1
]}

Hu, Honggang ^{[1
]}

Zhao, Qingjie ^{[1
]}

Wu, Qiuye ^{[1
]}

Zhang, Dazhi ^{[1
]}

Jiang, Yuanying ^{[2
]}

Sun, Qingyan ^{[1
]}

机构：

[1] Second Mil Med Univ, Coll Pharm, Dept Organ Chem, Shanghai 200433, Peoples R China

[2] Second Mil Med Univ, Coll Pharm, Dept Pharmacol, Shanghai 200433, Peoples R China

[3] Second Mil Med Univ, Overseas Educ Fac, Shanghai 200433, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 07期

基金：

中国国家自然科学基金;

关键词：

Synthesis; 1H-1,2,4-triazol-5(4H)-one derivatives; Antifungal evaluation; LANOSTEROL; 14-ALPHA-DEMETHYLASE; AZOLE ANTIFUNGALS; CYTOCHROME-P450; DERIVATIVES; AGENTS; CYP51;

D O I：

10.1016/j.ejmech.2011.02.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based on the structure of the active site of cytochrome P450 14 alpha-demethylase (CYP51) and the conclusions of the structure-activity relationships of azole antifungals, a series of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one of fluconazole analogs was synthesized. All compounds were characterized by IR, HRMS, (HNMR)-H-1 and C-13 NMR spectroscopic analysis. Results of preliminary antifungal in vitro test using eight human pathogenic species showed that some compounds displayed comparable or even better antifungal activities than reference drug fluconazole and that compound 3i exhibited significant activity against Candida albicans being worthy of further optimization. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：3135 / 3141

页数：7

共 17 条

[1]

Aoyama Y, 1996, J BIOCHEM-TOKYO, V119, P926

[2]

Calderone RA, 2012, Candida and candidiasis

[3] Design, synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P450 14α-demethylase [J].

Chai, Xiaoyun ;

Zhang, Jun ;

Hu, Honggang ;

Yu, Shichong ;

Sun, Qingyan ;

Dan, Zhigang ;

Jiang, Yuanying ;

Wu, Qiuye .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (05) :1913-1920

[4]

de Pauw E. Ben, 2008, ANTIMICROB AGENTS, V32, pS167

[5]

FISCHER RT, 1991, J BIOL CHEM, V266, P6124

[6] Epidemiology of nosocomial fungal infections [J].

Fridkin, SK ;

Jarvis, WR .

CLINICAL MICROBIOLOGY REVIEWS, 1996, 9 (04) :499-&

[7] Antifungal agents: Chemotherapeutic targets and immunologic strategies [J].

Georgopapadakou, NH ;

Walsh, TJ .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1996, 40 (02) :279-291

[8]

Helen L., 2006, BLOOD REV, V20, P267

[9] A three-dimensional model of lanosterol 14α-demethylase of Candida albicans and its interaction with azole antifungals [J].

Ji, HT ;

Zhang, WN ;

Zhou, YJ ;

Zhang, M ;

Zhu, J ;

Song, YL ;

Lü, J ;

Zhu, J .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (13) :2493-2505

[10]

Krishnamurthy N., 1998, US Patent, Patent No. 5728834

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