Design, synthesis and biological evalution of liguzinediol acetyl amino acid dual ester prodrugs as promissing inotropic agents
SHEN Min-zhe
LI Zhi
LI Wei
WEN Hong-mei
LIU Jian
ZHU Hao-hao
QIAN Cheng-bo
CAI Jian-guo
Abstract：Objective:Design and synthesis acetyl amino acid dual ester prodrugs of liguzinediol,investigate the chemical stability and physicochemical properties,and study the pharmacokinetic both in vitro and in vivo to find a suitable agent.Methods:Liguzinediol was coupled with each acetyl amino acid via the DMAP-catalyzed and DCC-condensated.The structure was characterized by LC-MS,1H-NMR and 13C-NMR.HPLC method was used to test the chemical stability,capacity factor,solubility,hpophilicity,and in vitro bioconversion and in vivo pharmacokinetic of various parameters of all prodrugs.Results:N-acetyl-L-valine,N-acetyl-L-leucine and N-acetylL-isoleucine dual ester released liguzinediol too slow to be a controlled prodrug.The solubility of N-acetyl-Lphenylalanine dual ester was poor.Among the eight prodrugs,N-acetylglycine dual ester not only released liguzinediol moderately but also showed highly chemical stability.Conclusion:The N-acetylglycine dual ester may be a promising prodrug with the advantages of highly chemical stability and moderate releasing rate.
Keywords：liguzinediolacetyl amino aciddual ester prodrugphysicochemical propertiespharmacokinetic
Publication Date：2017-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：7( 548-554 )