This survey of the impact of fluorine on medicinal chemistry highlights that fluorinated molecules have accounted for about 5-15 % of approved drugs over the course of decades. Fluorine has often replaced hydrogen or oxygen in earlier lead compounds and retained effectiveness. The ability of fluorine to make interactions with proteins and to affect pKas is discussed and some of the methods for introducing fluorine into a lead molecule are highlighted. Some case studies of drugs that benefit from a fluorine (either by improved pharmacokinetics or potency) are showcased and a final section suggests that introducing fluorine could reduce metabolism sufficiently to make drugs that are excreted intact into the environment; our own findings suggest that this latter effect is not really to be expected – fluorination increases metabolism as often as it decreases it when a comprehensive survey is made using matched molecular pairs: https://pubs.acs.org/doi/10.1021/jm0605233
“The many roles for fluorine in medicinal chemistry” by Hagmann.
J. Med. Chem.(2008)51, 15, 4359-4369
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