FDA-Approved Trifluoromethyl Group-Containing Drugs: A Review of 20 Years

Abstract

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.

Synthesis of (4-Trifluoromethyl)isoxazoles through a Tandem Trifluoromethyloximation/Cyclization/Elimination Reaction of α,β-Unsaturated Carbonyls

“…Compound X showed considerable inhibition of proliferation of MCF7 and HeLa cells (IC 50 = 19.5 and 39.2 μM, respectively) . Since trifluoromethylated molecules usually show superior chemical, physical, and biological activities in comparison to its nonfluoroalkylated counterpart, we believe that 8 would be an interesting candidate for anticancer evaluation and further medicinal applications.…”

“…Isoxazole, ranked 33rd in frequency among the 351 ring systems found in marketed drugs, is undoubtedly a highly important heterocyclic framework and a critical pharmacophore with a variety of biological activities such as anticancer, antibacterial, antifungal, antituberculosis, antidepressants, antirheumatic, anti-inflammatory, immunomodulatory, antialzheimer, and antidiabetic activities . On the other hand, incorporation of a trifluoromethyl (−CF 3 ) group in an organic molecule dramatically alters its physical, chemical, and biological properties such as lipophilicity, binding selectivity, metabolic stability, and bioavailability . Hence, isoxazoles bearing a trifluoromethyl group are more promising candidates to develop better pharmaceuticals or therapeutics.…”

Handling Fluorinated Gases as Solid Reagents Using Metal–Organic Frameworks

“…4B). Trifluoromethyl groups are ubiquitous in drugs (67), representing ~19% of fluorinated pharmaceuticals (68). TFMI represents an inexpensive and safe reagent for generating trifluoromethyl radicals (16,(69)(70)(71)(72).…”

Stereoselective synthesis of CF3-containing spirocyclic-oxindoles using N-2,2,2-trifluoroethylisatin ketimines: an update

“…6 Approximately 20% of the top-selling small drug molecules and 30% of agrochemicals available on the market comprises one or more uorine atoms in their structure, with the tri-uoromethyl group being the most prevalent. 7 The presence of uorine efficiently inuences the properties of a drug molecule via strong polar interactions. 6 Aer the hydrogen (H) atom, uorine (F) is the second smallest and most highly electronegative atom in the periodic table.…”