Alaoui Abdessamad El, Saha Nabendu, Schmidt Frédéric, Monneret Claude, Florent Jean-Claude
UMR 176 CNRS/Institut Curie, Centre de Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Bioorg Med Chem. 2006 Jul 15;14(14):5012-9. doi: 10.1016/j.bmc.2006.03.002. Epub 2006 Mar 22.
Two new glucuronide paclitaxel prodrugs have been synthesized. Linked to the 2'-OH of the drug by a carbonate function, they include a self-immolative spacer bearing an arylnitro or arylamino group between the drug and the glucuronic acid residue. Both prodrugs were well detoxified and easily cleaved in the presence of beta-D-glucuronidase with fast removal of the spacer, releasing paclitaxel. The arylamino spacer-containing prodrug, more stable than the corresponding nitro analogue, was selected for further studies.
已合成了两种新的紫杉醇葡糖醛酸苷前药。它们通过碳酸酯官能团与药物的2'-OH相连，在药物和葡糖醛酸残基之间包含一个带有芳基硝基或芳基氨基的自毁型间隔基。两种前药在β-D-葡糖醛酸酶存在下均能很好地解毒并易于裂解，间隔基快速去除，释放出紫杉醇。选择含芳基氨基间隔基的前药进行进一步研究，其比相应的硝基类似物更稳定。
