Synthesis of enantiomerically pure perhydro-1,4-diazepine-2,5-dione and 1,4-piperazine-2,5-dione derivatives exhibiting potent activity as apoptosis inhibitors.
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.
Department of Chemical and Biomolecular Nanotechnology, Instituto de Química Avanzada de Cataluña, Consejo Superior de Investigaciones Científica, J. Girona 18, 08034 Barcelona, Spain.
Alejandra
A
Moure
Mar
M
Orzáez
Mónica
M
Sancho
Angel
A
Messeguer
D017209:Apoptosis / Q000187:drug effects; D053478:Apoptosomes / Q000037:antagonists & inhibitors / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D057786:Peptidomimetics; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
D053478:Apoptosomes; D053477:Apoptotic Protease-Activating Factor 1; D001381:Azepines; D057786:Peptidomimetics; D010879:Piperazines; D011994:Recombinant Proteins; D000077489:Piperazine