Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics

A novel series of
optically active 2,6-disubstituted alkylphenols
with improved anesthetic profiles compared to widely used propofol
were synthesized. The incorporation of the cyclopropyl group not only
increased the steric effect but also introduced stereoselective effects
over their anesthetic properties. Compounds 1, 2, and 6 were selected as potential candidates
for further preclinical development including studies of their water-soluble
prodrugs. Clinical studies of candidate compound 6 (Haisco
HSK3486) as a general anesthetic are being performed in Australia
and China.