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http://dx.doi.org/10.5012/bkcs.2012.33.8.2597

The Design and Synthesis of 1,4-Substituted Piperazine Derivatives as Triple Reuptake Inhibitors  

Han, Min-Soo (Organic Chemistry Laboratory, Korea Institute of Science and Technology)
Han, Young-Hue (Organic Chemistry Laboratory, Korea Institute of Science and Technology)
Song, Chi-Man (Organic Chemistry Laboratory, Korea Institute of Science and Technology)
Hahn, Hoh-Gyu (Organic Chemistry Laboratory, Korea Institute of Science and Technology)
Publication Information
Bulletin of the Korean Chemical Society / v.33, no.8, 2012 , pp. 2597-2602 More about this Journal
Abstract
Novel 1,4-substituted piperazine derivatives 5, Series A and B were designed by fragment analysis and molecular modification of 4 selected piperazine-containing compounds which possess antidepressant activity. We synthesized new 39 analogues of Series A and 10 compounds of Series B, respectively. The antidepressant screening against DA, NE, and serotonin neurotransmitter uptake inhibition was carried out using the Neurotransmitter Transporter Uptake Assay Kit. The compounds in Series B showed relatively higher reuptake inhibitory activity for SERT, NET, and DAT than those in Series A. The length of spacer between the central piperazine core and the terminal phenyl ring substituted at the piperazine ring in Series B seems to exert an important role in the activity.
Keywords
Major depressive disorder; Antidepressants; Triple reuptake inhibitor; Piperazine; CNS drug;
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1 Welsch, M. E.; Snyder, S. A.; Stockwell, B. R. Curr. Opin. Chem. Biol. 2010, 14, 347.   DOI
2 Gray, D. L.; Xu, W.; Campbell, B. M.; Dounay, A. B.; Barta, N.; Boroski, S.; Denny, L.; Evans, L.; Stratman, N.; Probert, A. Bioorg. Med. Chem. Lett. 2009, 19, 6604.   DOI
3 Carter, D. S.; Cai, H.-Y.; Lee, E. K.; Iyer, P. S.; Lucas, M. C.; Roetz, R.; Schoenfeld, R. C.; Weikert, R. J. Bioorg. Med. Chem. Lett. 2010, 20, 3941.   DOI
4 Glowa, J. R.; Wojnicki, F. H. E.; Matecka, D.; Bacher, J. D.; Mansbach, R. S.; Balster, R. L.; Rice, K. C. Exp. Clin. Psychopharmacol. 1995, 3, 219.   DOI
5 Prisinzano, T.; Rice, K. C.; Baumann, M. H.; Rothman, R. B. Curr. Med. Chem.:Central Nervous Syst. Agents 2004, 4, 47.   DOI
6 Khan, A. Expert Opin. Investig. Drugs 2009, 18(11), 1753.   DOI
7 Kim, J. Y.; Kim, D.; Kang, S. Y.; Park, W.-K.; Kim, H. J.; Jung, M. E.; Son, E.-J.; Pae, A. N.; Kim, J.; Lee, J. Bioorg. Med. Chem. Lett. 2010, 20, 6439.   DOI
8 Kerns, E.; Di, L. Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization; Elsevier: Amsterdam, 2008; p 122.
9 Pardridge, W. M. J. Neurochem. 1998, 70, 1781.
10 Pajouhesh, H.; Lenz, G. R. Neurotherapeutics 2005, 2, 541.   DOI
11 Sonda, S.; Kawahara, T.; Murozono, T.; Sato, N.; Asano, K.; Haga, K. Bioorg. Med. Chem. 2003, 11, 4225.   DOI
12 Jorgensen, S.; Nielsen, E. O.; Peters, D.; Dyhring, T. Journal of Neuroscience Methods 2008, 169, 168.   DOI
13 Prins, J.; Olivier B.; Korte, S. M. Expert Opin. Investig. Drugs 2011, 20(8), 1107.   DOI
14 Holtzheimer, P. E., III.; Nemeroff, C. B. Neurotherapeutics 2006, 3, 42.   DOI
15 Kulkarni, S. K.; Dhir, A. Expert Opin. Investig. Drugs 2009, 18(6), 767.   DOI
16 Millan, M. J. Neurotherapeutics 2009, 6, 53.   DOI
17 Skolnick, P.; Basile, A. S. Drug Discov. Today: Ther. Strat. 2006, 3(4), 489.   DOI
18 Zisook, S.; Rush, A. J.; Haight, B. R.; Clines, D. C.; Rockett, C. B. Biol. Psychiatry 2006, 59, 203.   DOI
19 Papakostas, G. I.; Worthington, J. J., III.; Iosifescu, D. V.; Kinrys, G.; Burns, A. M.; Fisher, L. B.; Homberger, C. H.; Mischoulon, D.; Fava, M. Depress. Anxiety 2006, 23, 178.   DOI
20 Fava, M. J. Clin. Psychiatry 2001, 62(18), 4.
21 Prica, C.; Hascoet, M.; Bourin, M. Behav. Brain. Res. 2008, 194, 92.   DOI
22 Beer, B.; Stark, J.; Krieter, P.; Czobor, P.; Beer, G.; Lippa, A.; Skolnick, P. J. Clin. Pharmacol 2004, 44(12), 1360.   DOI
23 Skolnick, P.; Popik, P.; Janowsky, A.; Beer, B.; Lippa, A. S. Life Sciences 2003, 73, 3175.   DOI
24 Chen, Z.; Skolnick, P. Expert Opin. Investig. Drugs 2007, 16(9), 1365.   DOI   ScienceOn
25 Domling, A.; Huang, Y. Synthesis 2010, 17, 2859.