Synthesis,pharmacokinetics and in vivo antifungal activity of the novel water-soluble prodrugs of itraconazole analogue YL-24

被引：2

作者：

Yu Liu ^{[1
]}

XuFeng Cao ^{[1
]}

Xin Liu ^{[1
]}

YongBing Cao ^{[2
]}

WenJing Chu ^{[3
]}

YuShe Yang ^{[3
]}

机构：

[1] State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences

[2] School of Pharmacy,Second Military Medical University

[3] State Key Laboratory of Drug Research,Shanghai Institute of Materia Medico,Chinese Academy of Sciences

来源：

Chinese Chemical Letters | 2013年 / 24卷 / 04期

关键词：

Synthesis; Antifungal; Water-soluble prodrugs; Itraconazole analogue;

D O I：

暂无

中图分类号：

TQ460.1 [基础理论];

学科分类号：

1007 ;

摘要：

<正>To improve the aqueous solubility of an itraconazole analogue,compound 1(YL-24),a series of novel prodrugs were synthesized.Among these prodrugs,the phosphate disodium salt compound 7 exhibited excellent aqueous solubility(9.8 mg/mL) at near-neutral pH and sufficient stability in buffer solutions, along with favorable pharmacokinetic profiles.In particular,compounds 1 and 7 provided moderate survival efficacy in murine systemic Candida albicans SC5314 infection model,but their efficacy was weaker than that of fluconazole.

引用

页码：321 / 324

页数：4

共 6 条

[1] 抗真菌药物氟康唑研究新进展 [J].

万昆 ;

张奕奕 ;

周成合 ;

周向东 ;

耿蓉霞 ;

吉庆刚 .

中国抗生素杂志, 2012, 37 (01) :8-15+20

[2]

Design and synthesis of novel triazole antifungal derivatives based on the active site of fungal lanosterol 14a-demethylase(CYP51)[J]. Zhi Gang Dan,Jun Zhang,Shi Chong Yu,Hong Gang Hu,Xiao Yun Chai, Qing Yan Sun,Qiu Ye Wu~* Department of Organic Chemistry,School of Pharmacy,Second Military Medical University,Shanghai 200433,China.Chinese Chemical Letters. 2009(08)

[3]

Design and synthesis of pyridine-substituted itraconazole analogues with improved antifungal activities, water solubility and bioavailability[J] . Yu Liu,Zining Liu,Xufeng Cao,Xin Liu,Huili He,Yushe Yang.Bioorganic & Medicinal Chemistry Letters . 2011 (16)

[4] Recent patents in antifungal agent discovery [J].

Di Santo, Roberto .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2008, 18 (03) :275-292

[5]

Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations[J] . Aperis,Mylonakis.Expert Opinion on Investigational Drugs . 2006 (6)

[6]

Voriconazole: review of a broad spectrum triazole antifungal agent[J] . Kofla,Ruhnke.Expert Opinion on Pharmacotherapy . 2005 (7)

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