Publication Date:
2007-09-29
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Klaus -- Faeh, Christoph -- Diederich, Francois -- New York, N.Y. -- Science. 2007 Sep 28;317(5846):1881-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pharmaceuticals Division, Discovery Chemistry, F. Hoffmann-La Roche, CH-4070 Basel, Switzerland. klaus.mueller@roche.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17901324" target="_blank"〉PubMed〈/a〉
Keywords:
Biological Availability
;
Carbon/chemistry
;
Chemistry, Pharmaceutical
;
Chemistry, Physical
;
Databases, Protein
;
Fluorine/*chemistry/metabolism
;
Hydrogen-Ion Concentration
;
Ligands
;
Molecular Conformation
;
Molecular Structure
;
*Pharmaceutical Preparations/chemistry/metabolism
;
Pharmacokinetics
;
Pharmacology
;
Physicochemical Phenomena
;
Protein Binding
;
Proteins/chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink