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.