Synthesis, biological evaluation, and pharmacokinetic study of novel liguzinediol prodrugs.

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.