title: 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.
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.
authors.affiliation: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: S
authors.initials: S
authors.lastname: Niwayama
authors.forename: C
authors.initials: C
authors.lastname: Loh
authors.forename: B E
authors.initials: BE
authors.lastname: Turk
authors.forename: J O
authors.initials: JO
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Miyachi
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C100913:tetrafluorothalidomide; D013792:Thalidomide