Design, Synthesis, and Activity Study of Water-Soluble, Rapid-Release Propofol Prodrugs.

In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma while preserving its safety. In animal experiments, prodrugs (, , and ) were significantly better than fospropofol (the only water-soluble propofol prodrug that has been used clinically) in terms of safety, onset, and duration time of anesthesia.