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

Expert Opinion on Drug Metabolism & Toxicology
Cormac D Murphy, Graham Sandford

Abstract

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 no...Continue Reading

References

Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·H LaubleC D Stout
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·B K ParkP M O'Neill
Mar 22, 2002·Nature·David O'HaganCormac D Murphy
Apr 16, 2003·Accounts of Chemical Research·Stephen J Blanksby, G Barney Ellison
Dec 30, 2003·Journal of Medicinal Chemistry·John W Clader
May 4, 2004·Chembiochem : a European Journal of Chemical Biology·Grégori GerebtzoffAnna Seelig
Apr 1, 1994·Natural Product Reports·D B Harper, D O'Hagan
Jul 2, 2004·Organic Letters·Tatiana A Sergeeva, William R Dolbier
Feb 12, 2005·Angewandte Chemie·Ralph PauliniFrançois Diederich
Dec 1, 2005·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J ShangM G Beconi
Dec 13, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Myriam Malet-MartinoRobert Martino
Sep 29, 2007·Science·Klaus MüllerFrançois Diederich
Jan 17, 2008·Chemical Society Reviews·Sophie PurserVéronique Gouverneur
Apr 15, 2008·Angewandte Chemie·Alessandra S Eustáquio, Bradley S Moore
Jul 11, 2008·The Journal of Biological Chemistry·Matthew J BottomleyAndrea Carfí
Nov 18, 2008·Nature Chemical Biology·Andrea RentmeisterRudi Fasan
Feb 6, 2009·Organic & Biomolecular Chemistry·Stephen MoranCormac D Murphy
Apr 16, 2009·Environmental Toxicology and Chemistry·Derek A Jackson, Scott A Mabury
Oct 2, 2009·Organic & Biomolecular Chemistry·Peter WipfErin E Milner
Jan 21, 2010·Journal of Natural Products·Alessandra S EustáquioBradley S Moore
Jul 24, 2010·Chemico-biological Interactions·Olivier BarbierLuz María Del Razo
Jan 18, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Robert A WermersThomas P Moyer
Feb 26, 2011·Angewandte Chemie·Muthiah ManoharanMartin Egli
Aug 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yining JiPhil S Baran
Sep 15, 2011·Beilstein Journal of Organic Chemistry·Jessica R BreenBhairavi Patel
Jan 10, 2013·Organic & Biomolecular Chemistry·Tara V BrightGraham Sandford
Apr 13, 2013·Journal of Chromatography. a·Tina KosjekEster Heath
Jul 23, 2013·Environmental Science and Pollution Research International·Emma KavanaghCormac D Murphy
Jan 23, 2014·Chembiochem : a European Journal of Chemical Biology·Hai DengDavid O'Hagan
Jan 30, 2014·ChemMedChem·Maxwell J ShaughnessyGraham Sandford
Mar 29, 2014·Angewandte Chemie·Shira D HalperinRobert Britton
Jun 7, 2014·Organic & Biomolecular Chemistry·Sheng HuangHai Deng

❮ Previous
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Citations

Aug 20, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·William Palmer-BrownCormac D Murphy
May 19, 2017·Journal of Chemical Information and Modeling·Christina de Bruyn KopsJohannes Kirchmair
Aug 10, 2018·Chemical Communications : Chem Comm·Chloé BatisseFrédéric R Leroux
Oct 13, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hui WangJiang Zheng
Feb 12, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Haitao HuPalaniappan Kulanthaivel
Apr 1, 2018·Biodegradation·Marta SaccomannoCormac D Murphy
Jun 27, 2019·Biodegradation·Zhi-Qing ZhaoYan-Mei Li
Feb 12, 2021·Journal of Labelled Compounds & Radiopharmaceuticals·Hung-Man YuYu Chang
Mar 18, 2020·Journal of Medicinal Chemistry·Benjamin M JohnsonNicholas A Meanwell
Mar 17, 2021·Chemical Reviews·Jianlin HanVadim A Soloshonok
May 7, 2021·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·Kenneth WuSunita Mathur
Jul 27, 2021·ACS Catalysis·Chibueze I Onyeagusi, Steven J Malcolmson
Sep 13, 2019·Organic Letters·John D HerszmanSiegfried R Waldvogel
Jul 26, 2017·Journal of the American Chemical Society·Jian-Bo WangManfred T Reetz
Feb 6, 2018·Journal of Medicinal Chemistry·Nicholas A Meanwell
Nov 14, 2019·Journal of the American Chemical Society·Ana KopernikuLaurel L Schafer

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