Niwayama S, Loh C, Turk B E, Liu J O, Miyachi H, Hashimoto Y
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Bioorg Med Chem Lett. 1998 May 5;8(9):1071-6. doi: 10.1016/s0960-894x(98)00171-1.
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.
邻苯二甲酰亚胺的全氟化导致其作为肿瘤坏死因子-α（TNF-α）产生抑制剂的效力显著提高。我们研究了几种四氟邻苯二甲酰亚胺和α-甲基沙利度胺（3）的对映体依赖性。只有3表现出显著的对映体依赖性活性。活性增强的关键结构决定因素是四氟邻苯二甲酰基，它赋予了更高的效力并改变了抑制机制。
