Fluorination methods for drug discovery and development

Abstract

Introduction: The pivotal role that the element fluorine plays in modulating the properties of bioactive molecules is reflected by the growth of its presence in approved drugs. In 1970, approximately 2% of drugs contained fluorine with this number rising to 25% by 2011. The synthetic chemistry regarding incorporation of fluorine into organic molecules has also evolved over this time with a paradigm shift from harsh, toxic, hazardous reagents utilized primarily by specialist vendors to new deoxyfluorination reagents and metal-mediated techniques capable of the precise introduction of fluorine into complex organic substrates under relatively mild conditions.

Areas covered: This review highlights the importance of fluorinated compounds in drug discovery, and provides an overview on the synthetic strategies and methodologies developed to access them both in discovery and development.

Expert opinion: The development of new reagents for the safe and precise regioselective fluorination of biologically relevant compounds particularly in drug discovery remains a contemporary challenge in organic chemistry. However, significant strides have been made with the development of new deoxyfluorination reagents and the emergence of practical metal-mediated fluorination techniques have enabled the goal of efficient late-stage fluorination of drug-like compounds to be realized, and the extension of these methods for PET-labelling is being investigated.

Keywords: Fluorine; PET (positron emission tomography); chemistry under microfluidic conditions; deoxyfluorination; drug discovery; fluorine-18; metal-mediated fluorination.