Abstract

Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all physical and adsorption, distribution, metabolism, and excretion properties of a lead compound. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on molecular conformation of the drug, has only recently begun. Here, we review experimental progress in this vein and add complementary analysis based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.

Keywords

FluorineChemistryBioavailabilityDrugSelectfluorIntuitionDocking (animal)Combinatorial chemistryBiochemical engineeringComputational biologyPharmacologyOrganic chemistryBiologyPsychologyMedicine

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Publication Info

Year
2007
Type
review
Volume
317
Issue
5846
Pages
1881-1886
Citations
6319
Access
Closed

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Klaus Müller, Christoph Faeh, François Diederich (2007). Fluorine in Pharmaceuticals: Looking Beyond Intuition. Science , 317 (5846) , 1881-1886. https://doi.org/10.1126/science.1131943

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DOI
10.1126/science.1131943