FLUORINE REACTIVITY INSTALL

PET has been used to study biochemical transformations, drug pharmacokinetics, pharmacodynamics and as a powerful and superior non-invasive diagnostic and scanning technique to survey living tissue in humans. In addition to its role in therapeutic agents, fluorine also has biomedical applications, such as 18F in positron emission tomography (PET). The selection of drugs mentioned will not be comprehensive but should illustrate some of the wide applications that fluorine can have. This paper will discuss these current strategies in further detail, with examples of drugs that have been developed for the above purposes. This can occur by direct interaction of fluorine with the protein or indirectly by influencing the polarity of other groups of the compound which interact with the protein. The current strategies for introducing fluorine atoms into molecules are centred on the following topics:įluorine substitution is being increasingly used to enhance the binding affinity of a compound to a target protein. Therefore this type of modification can induce altered biological responses of the molecule. At the same time however, the introduction of a fluorine atom significantly alters the physicochemical properties of the compound due to its high electronegativity.

Greater lipophilicity of fluorine compared to hydrogen.ĭespite the fact that fluorine is slightly larger than hydrogen, several studies have demonstrated that it is a reasonable hydrogen mimic and is expected to cause minimal steric perturbations with respect to the compound's mode of binding to a receptor or enzyme. Greater stability of the C–F bond compared to the C–H bond. The highly electron withdrawing property of fluorine. The relatively small size of the fluorine atom (van der Waals radius of 1.47 Å), comparable to hydrogen (van der Waals radius of 1.20 Å). Important factors to be considered when synthesising fluorine-containing compounds are: These include: anti-cancer agents, antidepressants, anti-inflammatory agents, anaesthetics and central nervous system drugs, and a number of review articles on different therapeutic classes of fluorine-containing agents have been published in recent years 2-6.įluorine substitution has been extensively investigated in drug research as a means of enhancing biological activity and increasing chemical or metabolic stability. Currently, many fluorinated compounds are synthesised routinely in pharmaceutical research and are widely used in the treatment of diseases.

Early work by Fried on 9α-fluoro-hydrocortisone acetate revealed how introduction of fluorine into an existing biologically active compound imparted beneficial properties to that compound. Traditional medicinal chemistry based on the use of natural compounds or closely related derivatives, where there is a low abundance of compounds containing fluorine, meant that fluorinated compounds were rare in medicinal chemistry until the 1970s. An examination of the role of fluorine in medicinal chemistry reveals that substitution of an organic compound with even a single fluorine atom or trifluoromethyl group located in a key position of a biologically active molecule can result in a profound pharmacological effect. This makes fluorine a unique atom that in turn has a profound effect when bound to carbon in small organic molecules.

FLUORINE REACTIVITY INSTALL

A major challenge moving forward will be how and where to install fluorine in a rational sense to best optimise molecular properties.įluorine is both small (van der Waals radius 1.47 Å) and the most highly electronegative element in the Periodic Table (3.98 Pauling scale).

The increasingly routine incorporation of fluorine atom(s) into drug candidates suggests a bright future for fluorine in drug discovery and development. This short review aims to bring together these various aspects of the use of fluorine in medicinal chemistry applications, citing selected examples from across a variety of therapeutic and diagnostic settings. A further emerging application of the fluorine atom is the use of 18F as a radiolabel tracer atom in the exquisitely sensitive technique of Positron Emission Tomography (PET) imaging. Increased binding affinity of fluorinated drug candidates to target protein has also been documented in a number of cases. Selective installation of fluorine into a therapeutic or diagnostic small molecule candidate can enhance a number of pharmacokinetic and physicochemical properties such as improved metabolic stability and enhanced membrane permeation. The small and highly electronegative fluorine atom can play a remarkable role in medicinal chemistry.

Fluorine reactivity