Department of Chemical and Biomolecular Nanotechnology, Instituto de Química Avanzada de Cataluña, Consejo Superior de Investigaciones Científica, J. Girona 18, 08034 Barcelona, Spain.
Bioorg Med Chem Lett. 2012 Dec 1;22(23):7097-9. doi: 10.1016/j.bmcl.2012.09.078. Epub 2012 Sep 29.
Apoptosis is the process of programmed cell death and plays a fundamental role in several human diseases. We have previously reported the synthesis of the perhydro-1,4-diazepine-2,5-dione and 1,4-piperazine-2,5-dione derivatives as racemic mixtures. Compounds 1 and 2 showed a potent in vitro and in cellular extracts antiapoptotic activity. In view that the chiral discrimination has been an issue in the development and use of pharmaceutical drugs, the present contribution reports the synthesis of enantiopure peptidomimetics 1 and 2. The biological evaluation of these enantiomers as apoptosis inhibitors is also reported.
细胞凋亡是程序性细胞死亡的过程，在多种人类疾病中起着至关重要的作用。我们之前已经报道了氢化 1,4-二氮杂环庚烷-2,5-二酮和 1,4-哌嗪-2,5-二酮衍生物的合成，这些化合物是外消旋混合物。化合物 1 和 2 表现出很强的体外和细胞提取物抗凋亡活性。鉴于手性识别一直是药物开发和使用中的一个问题，本贡献报告了对映纯肽模拟物 1 和 2 的合成。还报告了这些对映异构体作为凋亡抑制剂的生物学评价。
