TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION ENHANCING ACTIVITY OF SUBSTITUTED 3'-METHYLTHALIDOMIDE - INFLUENCE OF SUBSTITUENTS AT THE PHTHALOYL MOIETY ON THE ACTIVITY AND STEREOSELECTIVITY

The synthesis and tumor necrosis factor (TNF)-alpha production enhanci ng activity of substituted 3'-methyl-thalidomides on human leukemia ce ll line HL-60 stimulated with 12-O-tetradecanoyl-phorbol 13-acetate (T PA) are described, Though the introduction of an electron-donating ami no group at the phthaloyl moiety of alpha-methylthalidomides enhanced the activity, substituted alpha-methylthalidomides showed decreased st ereoselectivity as compared to that of non-substituted alpha-methyltha lidomide, The data indicates that the TNF-alpha production enhancing a ctivity of thalidomide derivatives depends on both the electronic-stat e of substituents at the fused benzene ring and the stereochemistry of the glutarimide moiety.