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 (3e, 3g, and 3j) 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. Their molar dose, onset time,
and anesthesia duration time were comparable to those of propofol,
helping to maintain the clinical benefits of propofol. The experimental
results showed the potential of such compounds as water-soluble prodrugs
of propofol.