Molecules 2011, 16(5), 4104-4121; doi:10.3390/molecules16054104
Article

Solid-Phase Synthesis of Arylpiperazine Derivatives and Implementation of the Distributed Drug Discovery (D3) Project in the Search for CNS Agents

Paweł Zajdel 1,* email, Joanna Król 1 , Katarzyna Grychowska 1 , Maciej Pawłowski 1 , Gilles Subra 2 , Gaël Nomezine 2 , Jean Martinez 2 , Grzegorz Satała 3 , Andrzej J. Bojarski 3 , Ziniu Zhou 4 , Martin J. O’Donnell 4  and William L. Scott 4,* email
1 Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, Kraków 30-688, Poland 2 Équipe Aminoacides Peptides et Protéines, Institut des Biomolécules Max Mousseron IBMM, UMR CNRS 5247, Faculté de Pharmacie, Université Montpellier I et II, 15 avenue Charles Flahault, Montpellier 34060, France 3 Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, Kraków 31-343, Poland 4 Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
* Authors to whom correspondence should be addressed.
Received: 13 April 2011; in revised form: 14 May 2011 / Accepted: 16 May 2011 / Published: 19 May 2011
(This article belongs to the Section Medicinal Chemistry)
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Abstract: We have successfully implemented the concept of Distributed Drug Discovery (D3) in the search for CNS agents. Herein, we demonstrate, for the first time, student engagement from different sites around the globe in the development of new biologically active compounds. As an outcome we have synthesized a 24-membered library of arylpiperazine derivatives targeted to 5-HT1A and 5-HT2A receptors. The synthesis was simultaneously performed on BAL-MBHA-PS resin in Poland and the United States, and on BAL-PS-SynPhase Lanterns in France. The D3 project strategy opens the possibility of obtaining potent 5-HT1A/5-HT2A agents in a distributed fashion. While the biological testing is still centralized, this combination of distributed synthesis with screening will enable a D3 network of students world-wide to participate, as part of their education, in the synthesis and testing of this class of biologically active compounds.
Keywords: Distributed Drug Discovery (D3); combinatorial chemistry; solid-phase synthesis; SynPhase Lanterns; long-chain arylpiperazines; succinimides; 5-HT1A; 5-HT2A receptor affinity

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Cite This Article

MDPI and ACS Style

Zajdel, P.; Król, J.; Grychowska, K.; Pawłowski, M.; Subra, G.; Nomezine, G.; Martinez, J.; Satała, G.; Bojarski, A.J.; Zhou, Z.; O’Donnell, M.J.; Scott, W.L. Solid-Phase Synthesis of Arylpiperazine Derivatives and Implementation of the Distributed Drug Discovery (D3) Project in the Search for CNS Agents. Molecules 2011, 16, 4104-4121.

AMA Style

Zajdel P, Król J, Grychowska K, Pawłowski M, Subra G, Nomezine G, Martinez J, Satała G, Bojarski AJ, Zhou Z, O’Donnell MJ, Scott WL. Solid-Phase Synthesis of Arylpiperazine Derivatives and Implementation of the Distributed Drug Discovery (D3) Project in the Search for CNS Agents. Molecules. 2011; 16(5):4104-4121.

Chicago/Turabian Style

Zajdel, Paweł; Król, Joanna; Grychowska, Katarzyna; Pawłowski, Maciej; Subra, Gilles; Nomezine, Gaël; Martinez, Jean; Satała, Grzegorz; Bojarski, Andrzej J.; Zhou, Ziniu; O’Donnell, Martin J.; Scott, William L. 2011. "Solid-Phase Synthesis of Arylpiperazine Derivatives and Implementation of the Distributed Drug Discovery (D3) Project in the Search for CNS Agents." Molecules 16, no. 5: 4104-4121.

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