Fluorine in medicinal chemistry

Abstract

Since its first use in the steroid field in the late 1950s, the use of fluorine in medicinal chemistry has become commonplace, with the small electronegative fluorine atom being a key part of the medicinal chemist's repertoire of substitutions used to modulate all aspects of molecular properties including potency, physical chemistry and pharmacokinetics. This review will highlight the special nature of fluorine, drawing from a survey of marketed fluorinated pharmaceuticals and the medicinal chemistry literature, to illustrate key concepts exploited by medicinal chemists in their attempts to optimize drug molecules. Some of the potential pitfalls in the use of fluorine will also be highlighted.

Keywords: Conformational influences of fluorine; Fluorinated pharmaceuticals; Fluorine; Fluorine in medicinal chemistry; Impact of fluorine on lipophilicity; Impact of fluorine on pK(a); Impact of fluorine on physical properties; Molecular interactions of fluorine with proteins; Toxic metabolites containing fluorine.