Benzylphthalimides and phenethylphthalimides with thalidomide-like activity on the production of tumor necrosis...

Benzylphthalimide analogs (P1P's) and phenethylphthalimide analogs (P2P's) have been found to exhibit thalidomide-like activity on the production of tumor necrosis factor (TNF)-alpha by the human leukemia cell line, HL-60, stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA). Structure-activity relationships are discussed on the basis of the TNF-alpha production-enhancing activity. Benzylphthalimide (P1P-00) exhibited which is weaker than that of thalidomide, but introduction of a methyl group at the ortho-position of the benzyl moiety (P1P-10) resulted an increase to a level comparable with that of thalidomide. Phenethylphthalimide (P2P-00) is more potent than thalidomide, and its fluorinated derivative, 2-phenethyl-4,5,6,7-tetrafluoro-1H-isoindole-1,3-dione (FP2P-00), exhibited potent activity at very low concentrations.