As people around the world regard 2020 as the year of COVID-19, the medical community considers this year to be the second-best year, shared with the year 1996, with respect to the number of drug molecules approved by the US Food and Drug Administration (FDA). Both years, 2020 and 1996, had a record of 53 new drug molecules approved by the FDA. In the year 2020, 53 new chemical entities and 13 biological medicines were approved, including 10 monoclonal antibodies, 2 antibody-drug conjugates, 3 peptides, and 2 oligonucleotides. Among them, most of the compounds were found to have fluorine or fluorine-containing functional groups exhibiting numerous pharmacological activities. Herein, we summarized the trifluoromethyl (TFM, -CF₃)-group-containing FDA-approved drugs for the last 20 years. This article specially features and details the previous 20-year literature data, covering CF₃-incorporated potential drug molecules, including their syntheses and uses for various diseases and disorders. The review covers the detailed chemistry of 19 FDA-approved drugs in the past 20 years, which contains the TFM group as one of the pharmacophores.

Cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have been attracted as candidate treatments for Alzheimer's disease (AD). Fifteen khellactone-type coumarins from the roots ofPeucedanum japonicumThunberg were tested for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and MAO inhibitory activities. Compound 3′-angeloyl-4′-(2-methylbutyryl)khellactone (PJ13) most potently inhibited AChE (IC₅₀ = 9.28 µM), followed by 3′-isovaleryl-4′-(2-methylbutyroyl)khellactone (PJ15) (IC₅₀ = 10.0 μM). Compound senecioyl-4′-angeloyl-khellactone (PJ5) most potently inhibited BChE (IC₅₀ = 7.22 μM) and had the highest selectivity index (> 5.54), followed by 3′-senecioyl-4′-(2-methylbutyryl)khellactone (PJ10) and 3′,4′-disenecioylkhellactone (PJ4) (IC₅₀ = 10.2 and 10.7 μM, respectively). CompoundsPJ13,PJ15, andPJ5showed reversible and mixed-types of inhibition with K_ivalues of 5.98, 10.4 (for AChE), and 4.16 µM (for BChE), respectively. However, all 15 compounds weakly inhibited MAO-A and MAO-B. Molecular docking simulation revealed thatPJ13had a higher binding affinity (− 9.3 kcal/mol) with AChE thanPJ15(− 7.8 kcal/mol) orPJ5(− 5.4 kcal/mol), due to the formation of a hydrogen bond with Tyr121 (distance: 2.52 Å). On the other hand, the binding affinity ofPJ5(− 10.0 kcal/mol) with BChE was higher than forPJ13(− 7.7 kcal/mol) orPJ15(− 8.1 kcal/mol), due to the formation of a hydrogen bond with Ser198 (distance: 2.05 Å). These results suggest thatPJ13andPJ5are potential reversible selective inhibitors of AChE and BChE, respectively, for the treatment of AD.