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-HT_1A, 5-HT_2A 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-HT_1A receptors and moderate to low affinity for 5-HT_2A and 5-HT₇ sites [1].

The compounds examined in functional in vivo model behaved like postsynaptic 5-HT_1A 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.

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-HT_1A, 5-HT_2A 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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