The Fluorine Substituent Effect on Pharmacokinetics and Safety Profile from a Perspective of Medicinal Chemists

Abstract

Approximately 20% of pharmaceuticals contain fluorine atoms, and fluorine atoms are essential atoms for drug discovery. This is because the fluorine atom is about the same size as the hydrogen atom, so it functions as a bioisostere of the hydrogen atom, and at the same time has unique characteristics such as high electronegativity, large binding energy, and high lipophilicity. The introduction of fluorine atoms can regulate biological activities, pharmacokinetics, physicochemical properties, and toxicity, which are important as pharmaceuticals, by enhancing interactions with target proteins, increasing acidity, decreasing basicity, improving metabolic stability, and improving membrane permeability, etc. In this presentation, I would like to introduce actual examples of how we, medicinal chemists, utilize the characteristics of the fluorine atom to improve the completion of pharmaceuticals. In addition, we will also introduce cases where unexpected effects occur due to the introduction of fluorine.