Next generation organofluorine containing blockbuster drugs

[Display omitted] •Selected organofluorine-containing blockbuster drugs were profiled.•General aspects of the biological properties of these compounds were briefly introduced.•The synthetic methods for preparation of these organofluorine-containing drugs were presented. The role of organo-fluorine compounds in modern health, food and energy related industries is widely-appreciated. The unique properties that fluorine imparts to organic molecules, stemming from its high electronegativity and stability when bound to carbon, finds it increasingly being used in the development of new bioactivities. Around 25 % of the current blockbuster drugs contain fluorine and this number is increasing to well above 30 % for recent FDA approvals. In this Review we highlight a selection of the most successful organo-fluorine drugs, that have achieved blockbuster status, namely, sitagliptin (diabetes), sofosbuvir (hepatitis C), emtricitabine (HIV), glecaprevir/pibrentasvir (hepatitis C), elvitegravir (HIV), dolutegravir (HIV), bictegravir (HIV), efavirenz (HIV), enzalutamide (prostate cancer), aubagio (immunomodulatory) and paliperidone palmitate (schizophrenia). For each compound we discuss their discovery, their relevant disease state and how they are made, emphasizing the source of fluorine-containing moieties, and where known, their mode of action.