 HomeNewsWhat you need to know about fluoride-containing drugs

What you need to know about fluoride-containing drugs

2020-10-24

1597301952323

The application of fluorine chemistry in medicine can be traced back to the 1950s. In 1953, Dr. Josef Fried and Dr. Emily Sabo prepared a series of cortisone acetate derivatives and found that as a glucocorticoid, the anti-inflammatory activity of 9-fluoro substituted cortisone acetate was more than 10 times higher than the corresponding parent compound. It is the first public demonstration that the introduction of fluorine atoms in a specific position of a drug molecule can improve its biological activity.

In 1957, Dr. Robert Duczynski and others completed a series of studies on the synthesis, characterization and clinical trials of the nucleic acid antagonist 5-fluorouracil, which contributed to a breakthrough in cancer treatment.

The introduction of fluorine atoms or fluorine-containing groups into drug molecules can change the permeability and metabolic stability of drug molecules, adjust their pKa and fat solubility, and affect the absorption and distribution of drug molecules and the interaction with biological targets. Common means of drug screening.

Among the 38 small molecule drugs approved by the FDA in 2018, 18 are fluorine-containing drugs, such as Biktarvy for the treatment of HIV infection and Erleada (apalutamide) for the treatment of non-metastatic castration and anti-prostate cancer.
However, with the development and popularization of fluorine-containing drugs, people still need to consider their chemical stability in the human body and the impact of metabolites produced by enzymes on the human body, as well as safety issues during administration and treatment. The carbon-fluorine bond has a high bond dissociation energy (BDE), indicating that the carbon-fluorine bond is not easy to split uniformly. However, under the action of nucleophiles and drug-metabolizing enzymes in the human body, certain types of C-F bonds can easily generate fluoride anion species through heterocleavage. Early clinical data showed that voriconazole, a broad-spectrum antifungal drug, can increase fluoride levels in human plasma. Fluoride has a strong affinity for Ca2 in bones, which can cause bone strength reduction, bone metabolism disorders, periostitis, osteochondroma and other diseases.
Recently, Dr. Pan Yue from NIBR summarized the possible metabolic pathways of fluorine-containing drugs with different structures in the human body in the "ACS Medicinal Chemistry Letters". Some drug molecules can be decomposed to produce fluoride and fluorine-containing toxic metabolites. Feasible suggestions are put forward for the improvement. Here, medicinal chemistry researchers are reminded to think carefully when designing related structural drugs.
At present, our company can produce a variety of high-purity fluorine-containing biomedical intermediate materials on a large scale: perfluorooctane, perfluorodecalin, perfluorooctyl bromide, perfluorooctyl ethyl acrylate, perfluorotripropylamine, all Fluorotributylamine, fluorosurfactant, etc.

Previous: Graphene, the protagonist of the next revolution in science and technology is it!

Next: Development of electronic special gas industry