Design, Synthesis and Druggability Evaluation of Liguzinediol Valine Ester Prodrug as Promissing Inotropic Agent
10.14148/j.issn.1672-0482.2017.0412
- VernacularTitle:Liguzinediol缬氨酸酯前药的设计、合成及成药性评价
- Author:
Zhi LI
1
;
Min-Zhe SHEN
;
Wei LI
;
Hong-Mei WEN
;
Jian LIU
;
Hao-Hao ZHU
;
Cheng-Bo QIAN
;
Jian-Guo CAI
Author Information
1. 南京中医药大学药学院
- Keywords:
liguzinediol;
prodrug;
physicochemical properties;
pharmacokinetics
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2017;33(4):412-416
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE One liguzinediol valine ester prodrug was synthesized and evaluated for the physicochemical properties and bioconversion,which laid the foundation for further study of liguzinediol amino acid ester prodrugs.METHODS Liguzinediol valine ester prodrug was prepared by a two-step reaction of condensation and deprotection from liguzinediol,and its structure was verified by LC-HRMS,1H-NMR and 13C-NMR.The chemical stability,capacity factor,solubility,lipophilicity,metabolic stability in human plasma and pharmacokinetics study in vivo of valine ester prodrug were tested by HPLC.RESULTS Liguzinediol valine ester prodrug retained great solubility and showed good bioconversion in human plasma.The half-time of liguzinediol was extended obviously.However,the lipophilicity was relatively poor.CONCLUSION Liguzinediol valine ester prodrug was provided with the feature to form the drug,and obvious extended the half-time of liguzinediol.Meanwhile,it indicated that prodrug strategy was feasible,which provided the way of experiment for liguzinediol prodrug research.
