Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity.

The replacement of oxygenated functionality (hydroxy and alkoxy) with a fluorine atom is a commonly used bioisosteric replacement in medicinal chemistry. In this paper, we use molecular matched-pair analysis to better understand the effects of this replacement on lipophilicity. It seems that the reduced log of the oxygenated compound is normally dominant in determining the size of this difference.