It is known, that many serotonin receptors ligands, especially 5-HT_1A and 5-HT_2A, posses antidepressant, anxiolitic and antipsychotic activity. As we reported in our previous paper [1] several 8-alkoxy derivatives of 1,3-dimethyl-7-[(4-phenylpiperazin-1-yl)- alkyl]-1H-purine-2,6(3H,7H)-dione have shown moderate to high affinity for 5-HT_1A (K_i = 11-19 nM), 5-HT_2A (K_i = 15-253 nM) and 5-HT₇ (K_i = 51-83 nM ) receptors, depending on the structure of moiety in the 7 position of 1H-purine-2,6(3H,7H)-dione. In our further studies in a group of 8-amino derivatives of 1,3-dimethyl-7- [(4-phenylpiperazin-1-yl) -alkyl]-1H -purine -2,6(3H,7H) -dione we have found out, that replacing the alkoxy substituent in the 8 position with amino substituent strongly decreases affinity for 5-HT_2A and 5-HT₇ receptors, but enhances affinity and selectivity for 5-HT_1A ones. In order to determine the influence of moiety in 8 position of 1H-purine- 2,6(3H,7H)-dione on the affinity for serotonin receptors we designed and synthesized 1,3-dimethyl-7 -[(4-phenylpiperazin-1-yl) -alkyl]-1H-purine -2,6(3H,7H)-dione derivatives possessing 8-acylamide substituent (Scheme 1).

The new 8-acylamide analogues are under pharmacological trials. The structure-activity relationship will be discussed.

[1] G. Chłoń-Rzepa, P. Żmudzki, P. Zajdel, A.J. Bojarski, B. Duszyńska, A. Nikiforuk, E. Tatarczyńska, M. Pawłowski: Bioorg. Med. Chem. 2007, 15, 5239-5250

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