Structure-5-HT receptor affinity relationship in a new group of 7-arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione.

In our previous paper, we have reported that some 8-alkoxy-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives possessed high affinity and displayed agonistic activity for the serotonin 5-HT1A receptor. In order to examine the influence of the substituent in the position 8 of the purine moiety on the affinity for the serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors, a series of 7-arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl (THIQ) derivatives of 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione were synthesized. All the final compounds were investigated in in vitro competition binding experiments for serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors. The structure-affinity relationships for this group of compounds were discussed. For selected compounds, functional assays for the 5-HT1A receptor were carried out. The results of the assays indicated that these groups of derivatives possessed antagonistic activity for this receptor.
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