Prodrugs activated by intramolecular cyclization:dipeptide esters of paracetamol

摘要

Paracetamol(1)is an analgesic and anti-pyretic drug,normally metabolized in the liver where it produces a toxic metabolite,benzoquinonimine,which leads to cellular death.So,the development of paracetamol prodrugs appears as a way to improve its stability and reduce its hepatotoxicity.The preparation of prodrugs generally involves a covalent bond between a drug and a carrier,leading to a chemical structure that allows drug delivery in vivo,which can occur through an enzymatic or chemical mechanism.We know that drug delivery through enzymatic mechanisms possesses some advantages.However,this type of delivery can be strongly affected by biological variability.Thus,dipeptide carriers appear as attractive drug carriers,because they can release the parent drug through an intramolecular cyclization to a diketopiperazine(DKP).