Halogens, particularly fluorine, chlorine, and bromine, play a pivotal role in modern drug discovery and development. Their incorporation into drug molecules significantly influences physicochemical properties, including lipophilicity, metabolic stability, and target binding affinity. Fluorine, the most commonly used halogen, enhances bioavailability and receptor interactions, as seen in several blockbuster drugs. Chlorine and bromine contribute to hydrophobic interactions and modulate pharmacokinetics, while iodine is less frequently utilized due to its larger atomic size and reactivity. The strategic placement of halogens in drug scaffolds has led to the success of numerous FDA-approved pharmaceuticals across therapeutic areas, including oncology, infectious diseases, and central nervous system disorders. This review explores the structure-activity relationships (SAR) of halogen-containing drugs, highlighting recent approvals (2025), their synthesis (with yields, when available), therapeutic use, and, when experimentally available, the interaction with their biological target macromolecules.

Fluorinated heterocycles have become fundamental structures in contemporary pharmaceutical chemistry, constituting around 25% of all drugs available on the market. This in-depth review explores the medicinal uses of fluorinated heterocycles, focusing particularly on three important classes: fluorinated quinolines, pyrazoles, and pyridines. Fluorinated quinolines, such as fluoroquinolone antibiotics, have transformed antimicrobial treatment by simultaneously inhibiting DNA gyrase and topoisomerase IV. Fluorinated pyrazoles, like celecoxib and its associated anti-inflammatory drugs, exhibit selective inhibition of cyclooxygenase-2 with enhanced therapeutic profiles. Fluorinated pyridines include a wide range of therapeutic applications, from antiviral medications like favipiravir to central nervous system drugs featuring trifluoromethylpyridine groups. The deliberate addition of fluorine enhances metabolic stability, bioavailability, and selectivity for targets while altering physicochemical characteristics that are vital for drug efficacy. Structure-activity relationship analyses illustrate how the positioning of fluorine substitution affects biological activity, with distinct patterns identified for each class of heterocycles. Despite their achievements, challenges persist including the emergence of resistance to fluoroquinolones and safety issues linked to certain fluorinated structures. Ongoing research emphasizes new synthetic techniques, combination treatments, and applic

Fluorine ions have transformed the manufacturing of modern medications and continue to dramatically change the physical, pharmacokinetic, and pharmacodynamic properties of drugs. The physical properties of carbon-fluorine bonds are unique due to the very high bond dissociation energy of this bond, and the fact that fluorine is a highly electronegative atom with minimal steric interference from bonding to a carbon atom, provide chemists with an opportunity to precisely modify the molecular properties of drugs without changing the overall framework of the molecule. Based on the above characteristics of C-F bonds, strategic fluorine incorporation into many biologically active molecules increases the molecules' lipophilicity, membrane permeability, metabolic stability, and resistance to enzymatic degradation, and therefore increases the bioavailability and half-life duration in vivo of those molecules. There is also a significant                   body of knowledge that demonstrates substituting fluorine atoms in drug molecules                  impacts the electronic distribution, conformation, and intermolecular interactions of those molecules, resulting in increased affinity and selectivity towards their intended targets. This review presents and discusses the influence of fluorine in drug design and highlights the influence of fluorine on molecular action via structural activity relationships as well as the method of synthesizing fluorinated drug molecules. Representative patient-indicated and commercially available fluorinated drug examples that have been clinically approved include fluoroquinolone antibiotics and fluorinated steroids used in the treatment of cancer, neurological, infectious, and cardiovascular diseases. The review additionally provides a discussion of emerging methodologies that utilize novel electrophilic and nucleophilic fluorination reagents, late stage fluorination strategies, and the incorporation of trifluoromethyl or perfluoroalkyl groups into drug structures for optimization of pharmacokinetic properties In summary, this review illustrates how the strategic fluorination is a key component of the expanded utility of chemical compounds to develop new drugs.

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding ability of fluorinated drug target proteins has also been reported in some cases. An emerging line of research on F substitution has been addressed by using 18F as a radiolabel tracer atom in the extremely sensitive methodology of positron emission tomography (PET) imaging. This review aims to report on the fluorinated drugs approved by the US Food and Drug Administration (FDA) from 2016 to 2022. It cites selected examples from a variety of therapeutic and diagnostic drugs. FDA-approved drugs in this period have a variety of heterocyclic cores, including pyrrole, pyrazole, imidazole, triazole, pyridine, pyridone, pyridazine, pyrazine, pyrimidine, triazine, purine, indole, benzimidazole, isoquinoline, and quinoline appended with either F-18 or F-19. Some fluorinated oligonucleotides were also authorized by the FDA between 2019 and 2022.

The insertion of fluorine atoms and/or fluoroalkyl groups can lead to many beneficial effects in biologically active molecules, such as enhanced metabolic stability, bioavailability, lipophilicity, and membrane permeability, as well as a strengthening of protein-ligand binding interactions. However, this "magic effect" of fluorine atom(s) insertion can often be meaningless. Taking advantage of the wide range of data coming from the quest for carbonic anhydrase (CA) fluorinated inhibitors, this Minireview attempts to give "general guidelines" on how to wisely insert fluorine atom(s) within an inhibitor moiety to precisely enhance or disrupt ligand-protein interactions, depending on the target location of the fluorine substitution in the ligand. Multiple approaches such as ITC, kinetic and inhibition studies, X-ray crystallography, and NMR spectroscopy are useful in dissecting single binding contributions to the overall observed effect. The exploitation of innovative directions made in the field of protein and ligand-based fluorine NMR screening is also discussed to avoid misconduct and finely tune the exploitation of selective fluorine atom insertion in the future.

due to the strength of the carbon–fluorine bond. Fluorine has no known metabolic role in mammals, but a few plants and marine sponges synthesize organofluorine Fluorine is a chemical element; it has the symbol F and atomic number 9. It is the lightest halogen and exists at standard conditions as pale yellow diatomic gas. Fluorine is extremely reactive as it reacts with all other elements except for the light noble gases. Fluorine in its elemental form is highly toxic. Among the elements, fluorine ranks 24th in cosmic abundance and 13th in crustal abundan Twenty percent of modern pharmaceuticals contain fluorine. One of these, the cholesterol-reducer atorvastatin (Lipitor), made more revenue than any other drug until it became generic in 2011. The combination asthma prescription Seretide, a top-ten revenue drug in the mid-2000s, contains two active ingredients, one of which – fluticasone – is fluorinated. Many drugs are fluorinated to delay inactivation and lengthen dosage periods because the carbon–fluorine bond is very stable. Fluorination also increases lipophilicity because the bond is more hydrophobic than the carbon–hydrogen bond, and this often helps in cell membrane penetration and hence bioavailability. Tricyclics and other pre-1980s antidepressants had…