Development of Novel Biological Response Modifiers Derived from Thalidomide
1999
There has been a resurgence of interest in thalidomide (N-α-phthalimidoglutarimide), a teratogenic hypnotic/sedative agent, in recent years due to its potential usefulness of the treatment of various diseases. The effectiveness of the drug has been attributed to its regulating activity on tumor necrosis factor alpha production. The regulating activity has been found to be bidirectional, depending on both cell-type and the cell-stimulator. The bidirectional activity was separated by structural development of the drug, resulting in novel, potent, and structurally new thalidomides. By further structural development, novel types of androgen antagonists and nonpeptide protease inhibitors have been derived. Some of the developed compounds have been found to elicit potent antiangiogenic activity and/or potent inhibitory activity on tumor cell invasion. The studies on these structural development and the expansion of biological activities is reviewed in relation to the structure-activity relationships.
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