The Latest FDA-Approved Pharmaceuticals Containing Fragments of Tailor-Made Amino Acids and Fluorine

Abstract

Nowadays, the selective introduction of fluorine into bioactive compounds is a mature strategy in the design of drugs allowing to increase efficiency, biological half-life and bio-absorption. On the other hand, amino acids (AAs) represent one of the most ubiquitious classes of naturally occurring organic compounds, which are found in over 40% of newly marked small-molecule pharmaceutical drugs and medical formulations. The primary goal of this work is to underscore two major trends in the design of modern pharmaceuticals. The first is dealing with the unique structural characteristics provided by the structure of amino acids featuring an abundance of functionality and the presence of a stereogenic center, all of which bodes well for the successful development of targeted bioactivity. The second is related to fine-tuning the desired activity and pharmacokinetics by selective introduction of fluorine. Historically, both trends were developed separately as innovative and prolific approaches in modern drug design. However, in recent decades, these approaches are clearly converging leading to an ever-increasing number of newly approved pharmaceuticals containing both structural features of amino acids and fluorine.

Pafolacianine, the magic wand of intraoperative imaging of folate-receptor positive ovarian cancer

“…The direct linkage of the folic acid with the NIR dye has been reported to result in the formation of unwanted enamine byproduct, which was avoided by replacing the amine bearing glutamate moiety of the folic acid with tyrosinate moiety (25). This replacement not only increased the stability of the desired product upon conjugation with S0456 dye, but tyrosinate linker also exhibited optimum optical properties compared to other amino acid linkers (24,25). The synthesis is shown in Figure 2, with the commercially available triflouroacetylpteroic acid as the starting material (24,25).…”

“…This replacement not only increased the stability of the desired product upon conjugation with S0456 dye, but tyrosinate linker also exhibited optimum optical properties compared to other amino acid linkers (24,25). The synthesis is shown in Figure 2, with the commercially available triflouroacetylpteroic acid as the starting material (24,25).…”

Design and synthesis of a clickable, photoreactive amino acid p-(4-(but-3-yn-1-yl)benzoyl)-l-phenylalanine for peptide photoaffinity labeling

“…With outstanding potency, selectivity and low toxicity, bioactive amino acid-containing compounds and peptides have been important sources of novel drug candidates. [1][2][3][4] The identication of their specic targets is the starting point for drug discovery and development. Photoaffinity labeling (PAL) is widely employed to identify the targets of bioactive molecules and to investigate ligand-receptor interactions within biological systems.…”

Enantiomeric N‐(tert‐Butylsulfinyl) Polyfluoroalkyl Aldimines in aza‐Henry Reaction: Effective Route to Chiral Polyfluoroalkyl Nitroamines and Diamines

“…The significant role of organofluorine compounds in various fields of science and industry is generally recognized. The introduction of a fluorine atom or a fluorinated group into a molecule to modify its physicochemical and biological properties has become an established concept in the design and development of new materials and pharmaceuticals [1a–e] . The fragments of (poly)fluoroalkyl amine derivatives have been identified in numerous bioactive molecules [1b] .…”