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

  • Bioorg Med Chem Lett. 1998 May 5;8(9):1071-6. doi: 10.1016/s0960-894x(98)00171-1.
S Niwayama  1 ,  C Loh ,  B E Turk ,  J O Liu ,  H Miyachi ,  Y Hashimoto
Affiliations
  • 1. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
PMID: 9871710 DOI: 10.1016/s0960-894x(98)00171-1
Abstract

Perfluorination of phthalimides leads to dramatically increased potency as inhibitors of TNF-alpha production. We examined the enantiodependence for several tetrafluorophthalimides and alpha-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.