The chiral switches of ‘profen’ NSAIDs
Chiral switches have been successful in two non-steroidal anti-inflammatory drugs (NSAIDs) – ibuprofen and ketoprofen. The switch of ibuprofen is based on chiral inversion; (±)- and (S)-ibuprofen can be viewed as being essentially bioequivalent’. Ibuprofen carries a stereogenic center in the propanoic acid side chain and exists as a pair of enantiomers. Dexibuprofen is (S)-(+)-Ibuprofen.
Chiral Inversion
COX inhibition resides exclusively in the (S)-enantiomer, as shown by in vitro studies in a wide range of test systems. However, the activities of the two enantiomers of many profens are essentially indistinguishable in vivo, due to the unidirectional metabolic bioconversion of the (R)-enantiomer to the (S)-enantiomer, referred to as chiral inversion. The extent of this inversion differs between compounds and species, and in some cases, the inactive (R)-enantiomers are pro-drugs for the active (S)-forms.
Nomenclature
(2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid
Lesson
Understanding metabolism guides the choice of right sinle enantiomer.
Exercise
Understand the phenomenon of chiral inversion
References
Israel Agranat, Hava Caner and John Caldwell, Nature reviews, Drug Discovery, 1, October,| 753-768, 2002.
Chiral switch. Wikipedia, Wikipedia Foundation, 201/08/2022. https://en.wikipedia.org/wiki/Chiral_switch
Lien Ai Nguyen, Hua He, and Chuong Pham-Huy, Chiral drugs: An overview, Int J. Biomed. Sci. 1,2,85-100, 2006; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614593/
