Acetaminophen, structure

Roberts, S.A., Veronica, F.P. and Jollow, D.J. (1990) Acetaminophen structure-toxicity studies In vitro covalent binding of a non-hepatotoxic analog, 3-hydroxy-acetanilide. Toxicology and Applied Pharmacology, 105, 195-208. 

The amide functional group is found repeated many times in natural proteins and some synthetic materials. For example, you may have used a nonaspirin pain reliever containing acetaminophen. In the acetaminophen structure shown below, you can see that the amide (-NH-) group connects a carbonyl group and an aromatic group. 

Roberts SA, Price VF, Jollow DJ. Acetaminophen structure-toxicity studies In vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide. Toxicol Appl Pharmacol 1990 105 195-208. 

FIGURE 25.29 (a) The structures of several commou analgesic agents. Acetaminophen is marketed under the tradename Tylenol. Ibuprofen is sold as Motrin, Nuprin, and Advil, (b) Acetylsalicylate (aspirin) inhibits the cyclooxygenase activity of endoperoxide synthase via acetylation (covalent modification) of Ser ... 

Observing and Inferring What structural shape do aspirin, acetaminophen, and ibuprofen have in common ... 

Predicting Predict the possibility of other medicines that might have the same common structural shape as aspirin, acetaminophen, and ibuprofen. 

Finally, a series of papers have been published on the solid state NMR spectra of a number of analgesic drugs. Jagannathan recorded the solid state 13C NMR spectrum of acetaminophen in bulk and dosage forms [60], From the solution-phase NMR spectrum, assignments of the solid state NMR resonances could be made in addition to explanations for the doublet structure of some resonances (dipolar coupling). Spectra of the dosage product from two sources indicated... 

Chandrasekharan, N. V., Dai, H., Roos, K. L. et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs cloning, structure, and expression. Proc. Natl Acad. Sci. U.S.A. 99 13926-13931,2002. 

An important analgesic, comparable to aspirin in structural complexity, is acetaminophen ... 

Ibuprofen has good analgesic and anti-inflammatory action. Ibuprofen is made at approximately 16 million Ib/yr in the U.S. Its price is higher than aspirin or acetaminophen and is usually around 9.30/lb. Its common name does tell us something about its structure. There are a number of profens, ... 

Bioactivation is a classic toxicity mechanism where the functional group or the chemical structure of the drug molecule is altered by enzymatic reactions. For example, the enzymatic breakdown of the analgesic acetaminophen (paracetamol), where the aromatic nature and the hydroxyl functionality in paracetamol are lost, yields A -acetyl-p-benzoquinone imine, a hepatotoxic agent. Paracetamol can cause liver damage and even liver failure, especially when combined with alcohol. 

Fig. 2.1. Illustrative example of a MOLFile for acetaminophen (also known as paracetamol), (a) Molecular structure of acetaminophen, commonly known as Tylenol. Tylenol is a widely used medicine for reducing fever and pain, (b) MOLFile for acetaminophen.

Propoxyphene (Schedule II) is another opiate prescribed for pain which is much weaker than those mentioned above. Notice the structural similarities to methadone. Its effects last longer than many other drugs in this class which means it can be taken less frequently and the potential of abuse will be lessened. It can also be formulated with aspirin or acetaminophen in order to have a summation effect. 

Oxycodone is available alone or in combination with either acetaminophen or aspirin. Its chemical structure is most closely related to codeine, but it has strong painkilling effects equal to those of morphine. 

Figure 18.8. Structures of acetaminophen and N-accty l-/ -bcnzoquinone imine (NAPQI) metabolites and GSH defense.

Figure 12.9. Structures of selected cyclooxygenase inhibitors. Rofeeoxib is selective for Cox-2 the selectivity of acetaminophen in vivo is not entirely clear yet. The residual inhibitors act on both Cox-1 and Cox-2.

Boldyreva, E. V., Shakhtshieder, T. P, Vasilchenko, M. A., Ahsbahs, H. and Uchtmann, H. (2000). Anisotropic crystal structure distortion of the monoclinic polymorph of acetaminophen at high hydrostatic pressures. Acta Crystallogr. B, 56, 299-309. [239]... 

With reference to the structures of acetylsalicylic acid (aspirin, Chapter 2 opening molecule) and acetaminophen (the active ingredient in Tylenol), explain each statement (a) Acetaminophen tablets can be stored in the medicine cabinet for years, but aspirin slowly decomposes over time (b) Children s Tylenol can be sold as a liquid (acetaminophen dissolved in water), but aspirin cannot. 

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