Fluorine in medicinal chemistry.
Fluorinated compounds are synthesized in pharmaceutical research on a routine basis and many marketed compounds contain fluorine. The present review summarizes some of the most frequently employed strategies for using fluorine substituents in medicinal chemistry. Quite often, fluorine is introduced to improve the metabolic stability by blocking metabolically labile sites. However, fluorine can also be used to modulate the physicochemical properties, such as lipophilicity or basicity. It may exert a substantial effect on the conformation of a molecule. Increasingly, fluorine is used to enhance the binding affinity to the target protein. Recent 3D-structure determinations of protein complexes with bound fluorinated ligands have led to an improved understanding of the nonbonding protein-ligand interactions that involve fluorine.
Böhm
Hans-Joachim
HJ
Discovery Research, Pharmaceuticals Division, Roche, CH 4070 Basel, Switzerland. hans-joachim.boehm@roche.com
Banner
David
D
Bendels
Stefanie
S
Kansy
Manfred
M
Kuhn
Bernd
B
Müller
Klaus
K
Obst-Sander
Ulrike
U
Stahl
Martin
M
D005461:Fluorine / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins; D005461:Fluorine