Design, synthesis, and bioavailability evaluation of coumarin-based prodrug of meptazinol

Based on the known coumarin-based prodrug system, a new meptazinol (Z)-3-[2-(propionyloxy) phenyl]-2-propenoic ester (3) was designed and synthesized as prodrug to minimize the first-pass effect of meptazinol (1) and improve the oral bioavailability. The prodrug (3) showed a 4-fold increase in oral bioavailability over the parent drug meptazinol in rats.

Graphical abstractA coumarin-based esterase-sensitive prodrug (3) of meptazinol (1) was designed and synthesized to minimize the first-pass effect of meptazinol. Biological evaluation results in rats indicated that there was a 4-fold increase in oral bioavailability of this prodrug compared to the parent drug meptazinol.Figure optionsDownload full-size imageDownload as PowerPoint slide