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Synthesis and serotonin receptors activity of new purine-2,6-dione derivatives with arylpiperazinylalkoxy moieties

Grażyna Chłoń-Rzepa 1Paweł Żmudzki 1Maciej Pawłowski 1Andrzej J. Bojarski 2Beata Duszyńska 2

1. Jagiellonian University, Medical College, Department of Pharmaceutical Chemistry, Medyczna 9, Kraków 30-688, Poland
2. Polish Academy of Sciences. Institute of Pharmacology, Smętna 12, Kraków 31-343, Poland

Abstract

For several years much attention has been focused on the functional importance of serotonin receptors in the pathogenesis of neuropsychiatric and other diseases. Among many classes of serotonin receptor ligands a long-chain arylpiperazines (LCAPs) containg a different amide/imide terminal fragment were mainly evaluated towards 5-HT1A, 5-HT2A and 5-HT7 receptors.

In our earlier studies it was shown that 7-arylalkyl derivatives of 1,3-dimethyl-3,7-dihydropurine-2,6-dione with 8-[3-(4-arylpiperazin-1-yl)-propylamino] moiety, displayed high to moderate affinity for 5-HT1A receptors and moderate to low affinity for 5-HT2A and 5-HT7 sites [1].

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The compounds examined in functional in vivo model behaved like postsynaptic 5-HT1A receptor antagonists [1].

To continue our research with this class of purine-2,6-dione analogues we designed and synthesized a novel series of arylpiperazines. Comparing to the previous work structural modifications consisted in replacing the amino group in the 8-position by a ether one.

przemysl25.JPG

The new compounds were synthesized in the reaction of previously obtained 1,3-dimethyl-7-arylalkyl-8-bromo-3,7-dihydro-purine-2,6-dione with the appropriate 3-(4-aryl-piperazin-1-yl)-propan-1-ol. The new analogues are under evaluation for their affinity for 5-HT1A, 5-HT2A and 5-HT7 receptors. The most active derivatives will be tested in in vivo behavioral models.

[1] G. Chłoń, M. Pawłowski, B. Duszyńska, A. Szaro, E. Tatarczyńska, A. Kłodzińska, E. Chojnacka-Wójcik: Pol. J. Pharmacol., 2001, 53, 359-368.

 

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Submitted: 2008-03-10 15:03
Revised:   2009-06-07 00:48