RT Journal Article
SR Electronic
T1 Fluorine in Pharmaceuticals: Looking Beyond Intuition
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1881
OP 1886
DO 10.1126/science.1131943
VO 317
IS 5846
A1 Müller, Klaus
A1 Faeh, Christoph
A1 Diederich, François
YR 2007
UL http://science.sciencemag.org/content/317/5846/1881.abstract
AB 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.