The use of isotopic substitution to delay the oxidative metabolism of the anesthetic propofol 1 was studied. The aromatic hydrogens of propofol 1 were replaced by deuterium to produce the mono-and trideuterated derivatives 4 and 5. In vitro metabolic studies on human hepatic microsomes showed no isotopic effect in the para hydroxylation of propofol, and 1, 4, and 5 display similar hypnotic activity and toxicity in mice.
