Fluorine as a key element in modern drug discovery and development
Organofluorine compounds are of paramount importance in modern chemical industry and have found wide application in crop protection, material science, and medicine as components of pharmaceutical agents. A persistent interest in fluorinated molecules is attributed to their advantageous chemical, physicochemical, and biological properties imparted by fluorine incorporation. Due to strong electron-withdrawing nature of fluorine and fluoroalkyl groups, they affect the physicochemical parameters of neighbouring substituents as well as of the whole molecule, including its reactivity, acidity, basicity and lipophilicity. Fluorination provides a convenient way of improving cell-penetration and making a molecule more easily delivered to the active site. Furthermore, it improves drug metabolic stability and toxicity and can have a direct effect on the binding to the active site of an enzyme or receptor due to the ability to form strong interactions via fluorine atoms with hydrogen bond donors, electron-poor functional moieties and lipophilic side-chains. Taking advantages of the fluorine and trifluoromethyl group, the most popular fluoroalkyl substituent, many essential drugs were rationally designed and developed, as for instance, breakthrough antiviral drugs Sofosbuvir and Voxilaprevir which are able to cure hepatitis C infection, anti-HIV drugs Efavirenz and Maraviroc, promising antimalarial drug candidate DSM265, anticancer kinase inhibitors Gefitinib and Vemurafenib, recently approved anticancer drug Enasidenib and many other. In this lecture the key role of fluorine in the discovery of these drugs will be highlighted and discussed.
LE STUDIUM RESEARCH FELLOW / Marie Skłodowska-Curie Research Fellow
Dr Volodymyr Sukach
FROM : Institute of Organic Chemistry of National Academy of Sciences of Ukraine - UA
IN RESIDENCE AT: Institute of Organic and Analytical Chemistry (ICOA) / CNRS, University of Orléans - FR