The active ingredient in Tylenol and many other painkillers is a drug known as acetaminophen (or sometimes paracetamol). Acetaminophen has been around for a long time and works pretty well, but it’s well known that this particular drug is highly toxic to the liver when taken in overdose or when the patient’s liver function is already compromised (this is why you do NOT take Tylenol for a hangover!). In the U.S., for example, acetaminophen is believed to be responsible for about half of all cases of acute liver failure.

Acetaminophen (top) and new potential replacements (bottom).

The liver toxicity occurs because liver enzymes metabolize the drug into a harmful compound known as an iminoquinone. This metabolization has nothing to do with the pain killing function of acetaminophen and so a drug which is not metabolized in this way but still works to reduce pain would be beneficial.

A recent publication in ACS Medicinal Chemistry Letters details preliminary attempts to synthesize analogues of acetaminophen which still work like acetaminophen but don’t generate toxic metabolites. These are based on tweaking the acetaminophen structure to add two heterocycles in place of the single benzene ring in the original structure.

The new drugs are still in the preliminary stages and it’s not yet known if they will work. There is a precedent, however, the even more popular painkiller ASA (i.e. Aspirin) is based on tweaking the structure of an older drug.