Synthesis,Biological Evaluation,and Pharmacokinetic Study of Novel Liguzinediol Prodrugs

LIU Zheng; LI Wei; WEN Hongmei; BIAN Huimin; CHEN Long; ZHANG Jing; CHEN Lei; YANG Kundi; FANG Qiuyue; CHEN Jing; FEI Yao

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Synthesis,Biological Evaluation,and Pharmacokinetic Study of Novel Liguzinediol Prodrugs

LIU Zheng #,LI Wei *,WEN Hongmei,BIAN Huimin,CHEN Long,ZHANG Jing,CHEN Lei,YANG Kundi,FANG Qiuyue,CHEN Jing,FEI Yao

School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210046

*Correspondence author

#Submitted by

Subject:

Funding: Major Scientific and Technological Special Project（No.2009ZX09103-081）, National Natural Science Foundation of China（No.81072542）, Specialized Research Fund for the Doctoral Program of Higher Education of China（No.20123237110010）

Opened online:25 April 2013

Accepted by: none

Citation: LIU Zheng,LI Wei,WEN Hongmei.Synthesis,Biological Evaluation,and Pharmacokinetic Study of Novel Liguzinediol Prodrugs[OL]. [25 April 2013] http://en.paper.edu.cn/en_releasepaper/content/4538183

Liguzinediol (LZDO) ester prodrugs (3, 4, 5) were synthesized and evaluated in vitro and in vivo for its potential use, with the aim of prolonging the half-life of the parent drug LZDO (1a) in vivo. Prodrug 3, 4, 5 were found to be a potent positive inotropic effect on the myocardium without the risk of arrhythmia. Prodrug 3, 4, 5 rapidly underwent enzymatic hydrolysis to release the parent compound LZDO in 1-3 h in rat liver microsomes and rat plasma. The half-life of the parent compound was prolonged after intragastric administering prodrug 3. Prodrug 3 was found to be a superior prodrug candidate for increasing myocardial contractility.

Keywords:Liguzinediol; Liguzinediol prodrugs; Synthesis; Positive inotropic effect; Pharmacokinetic.

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