The many roles for fluorine in medicinal chemistry

One cannot overestimate the profound influence that organofluorine chemistry has had on drug discovery. The ever increasing array of commercially available fluorinated starting materials coupled with novel and imaginative synthetic methodologies offers to the medicinal chemist broad opportunities to positively influence the direction and timelines in a drug discovery program. Medicinal chemists should approach the various structure-activity relationships that may need to be addressed with a keen understanding of the potential that selective fluorination may afford. That potential may be realized in solving issues as different as changes in solubility, CNS penetration, metabolic stability, or improvements in potency. A greater appreciation of the role(s) that fluorine substitution can have on the physicochemical properties in a molecule gives the medicinal chemist more strategies to solve some of their challenges in a drug discovery program. Hopefully, this Perspective and the few cited examples will provide incentives to further explore the opportunities in organofluorine chemistry as it relates to medicinal chemistry and drug discovery. © 2008 American Chemical Society.