title: Synthesis, biological evaluation, and pharmacokinetic study of novel liguzinediol prodrugs.
abstract: Liguzinediol (LZDO) ester prodrugs 3-5 were synthesized and evaluated in vitro and in vivo for their potential use in prolonging the half-life of the parent drug LZDO (1a) in vivo. Prodrugs 3-5 were found to display a potent positive inotropic effect on the myocardium, without the risk of arrhythmia. Prodrugs 3-5 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 administration of prodrug 3, which was found to be a superior prodrug candidate for increasing myocardial contractility.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210046, Jiangsu, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wen
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Bian
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Kun-Di
authors.initials: KD
authors.lastname: Yang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004355:Drug Stability; D006321:Heart / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D011719:Pyrazines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats
chemical_list: C572935:2,5-dihydroxymethyl-3,6-dimethylpyrazine; D011355:Prodrugs; D011719:Pyrazines