Cyclization-activated prodrugs. Synthesis, reactivity and toxicity of dipeptide esters of paracetamol

Dipeptide esters of paracetamol were prepared and observed to be quantitatively hydrolyzed to paracetamol and 2,4-diketopiperazines at pH 7.4 and 37 °C. Hydrolysis rates depended on dipeptide structure. These novel compounds do not affect the levels of hepatic glutathione.