Enhanced potency of perfluorinated thalidomide derivatives for inhibition of LPS-induced tumor necrosis factor-α production is associated with a change of mechanism of action

Perfluorination of phthalimides leads to dramatically increased potency as inhibitors of TNF-α production. We examined the enantiodependence for several tetrafluorophthalimides and α-methylthalidomide, 3. Only 3 exhibited strikingly enantiodependent activity. The key structural determinant for the enhanced activity is the tetrafluorophthaloyl group, which confers enhanced potency and a change in the mechanism of inhibition.