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Synthesis of New 5-Arylidene-1,3-thiazolidine-4-ones Bearing an (3-Aminopropylpiperazin-1-yl)propyl chain on N-3 Position by A "One-Pot Two Steps" Method under Microwave
* 1, 2 , 1, 2 , 3 , 2 , 2 , * 1
1  UNIVERSITE DE RENNES 1, Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, groupe ICMV, Bât.10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes Cedex. France
2  UNIVERSITE NANGUI ABROGOUA, Laboratoire de Chimie Bioorganique et de Substances Naturelles (LCBOSN), BP 802, Abidjan 02, République de Côte d'Ivoire
3  UNIVERSITE Péléforo Gon COULIBALY, UFR des Sciences Biologiques, BP 1328, Korhogo, Côte d'Ivoire

Published: 01 November 2016 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1

Protein kinases are enzymes assuring the transfer of a phosphate group of molecule donors of high energy, such as ATP, in specific substrates. The disorder of these enzymes in cellular environment are involved in some pathologies such as cancer and Alzheimer's disease [1]. So the discovery of inhibitors became the key point for the research of new therapeutic agents. In our team, N,N'-bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)aminopropylpiperazine (IC50=40 nM) was identified as promising and selective inhibitor [2, 3] of DYRK1A (dual specificity, tyrosine phosphorylation regulated kinases), a protein kinase of interest for neurodegenerative diseases [4, 5] and also for cancer [6]. In order to understand the mechanism of action of this inhibitor towards DYRK1A but also towards GSK3a/b (who also plays an important role in malaria), we have developed a 4-steps synthesis from the commercial reagents N,N'-bis(3-aminopropyl)piperazine. The key step of this process is the construction of the 2-thioxo-1,3-thiazolidine-4-one platform under microwave irradiation from commercial bis(carboxymethyl)trithiocarbonate. Results for the synthesis will be presented and discussed in this presentation .

1. Debdab M., Carreaux F., Renault S., Meijer L., Bazureau J.-P. et al. J. Med. Chem. 2011, 54, 4172.
2. Coulibaly W-K, Paquin L., Bénie A., Bekro Y-A., Durieu E., Meijer L., Bazureau J-P. Eur. J. Med. Chem. 2012, 58, 581.
3. Coulibaly W-K., Paquin L., Bénie A., Bekro Y-A., Durieux E., Rucheau S., Meijer L., Le Guével R., Corlu A., Bazureau J-P., Scienta Pharm. 2012, 80, 825.
4. Tahtouh T., Burgy G., Carreaux F., Bazureau J-P., Meijer L. et al. J. Med. Chem. 2012, 55, 9312-9330.
5. Burgy G., Limanton E., Meijer L., Carreaux F., Bazureau J-P. Eur. J. Med. Chem. 2013, 62, 728.
6. Ionescu A., Dufrasne F., Gelbcke M., Jabin I., Kiss R., Lamoral-Theys D. Mini-Rev. Med. Chem. 2012, 12, 1315.

Keywords: Microwave, Solution phase, 5-Arylidene rhodanine, Holmberg reaction, Koenevenagel condensation, One-pot two-steps, N-Boc carbamate, Trifuoroacetate salt