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Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):589-99. doi: 10.1517/17425255.2015.1020295. Epub 2015 Mar 2.

Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity.

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University College Dublin, UCD School of Biomolecular and Biomedical Science , Belfield, Dublin 4 , Ireland +353 1 7161311 ;



Fluorine's unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures.


This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the physicochemical characteristics of the element. Examples of more recently used larger scale synthetic methods for introduction of fluorine into drug leads are detailed and the potential for using biological systems for fluorinated drug production is discussed.


The synthetic procedures for carbon-fluorine bond formation largely still rely on decades-old technology for the manufacturing scale and new reagents and methods are required to meet the demands for the preparation of structurally more complex drugs. The improvement of in vitro and computational methods should make fluorinated drug design more efficient and place less emphasis on approaches such as fluorine scanning and animal studies. The introduction of new fluorinated drugs, and in particular those that have novel fluorinated functional groups, should be accompanied by rigorous environmental assessment to determine the nature of transformation products that may cause ecological damage.


biotransformation; fluorinating reagent; organofluorine; synthesis

[Indexed for MEDLINE]

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