An improved water-soluble prodrug of propofol with high molecular utilization and rapid onset of action

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

“…We conducted our experiment by following well-established methods for propofol prodrugs. , First, we tested the stability of prodrugs in water before the hydrolysis studies in plasma. The results suggested that 1a–1d were relatively stable in water (Supporting Information, Table S1).…”

“…X-series compounds are modified on the basis of the structure of HX0921 (Figure ). HX0921 is a propofol ester derivative with α-O from our previous research …”

“…HX0921 is a propofol ester derivative with α-O from our previous research. 18 In an in vitro experiment, HX0921 decomposed significantly faster in mouse plasma than fospropofol (Supporting Information, Table S2), which suggested that the introduction of heteroatoms in the α-position of the ester might accelerate the decomposition in vivo. In in vivo experiments, the propofol dose released from HX0921 at 2 × ED 50 was 74.0 mg/kg, which was lower than that from fospropofol (112.7 mg/kg).…”

“…The propofol prodrug remaining in the body continues to release the propofol, resulting in delayed wake-up and slow recovery. In our previous reports, we emphasized that the decomposition rate of propofol prodrugs and the molecular utilization of propofol were the key to the development of propofol prodrugs. For developing a more advantageous propofol prodrug, four series of prodrugs ( C-series , X-series , N-series , and O-series ) were synthesized and tested in this research (Figure ).…”