Two series of arylpiperazinyl-alkyl quinoline-, isoquinoline-, naphthalene-sulfonamides with flexible (13-26) and semi-rigid (33-36) alkylene spacer were synthesized and evaluated for 5-HT(1A), 5-HT(2A), 5-HT(6), 5-HT(7) and selected compounds for D(2), D(3), D(4) receptors. The compounds with a mixed 5-HT and D receptors profile 16 (N-{4-[4-(3-chlorophenyl)-piperazin-1-yl]-butyl}-3-quinolinesulfonamide) and 36 (4-(4-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-ethyl}-piperidine-1-sulfonyl)-isoquinoline), displaying antagonistic activity at 5-HT(7), 5-HT(2A), D(2) postsynaptic sites, produced antidepressant-like effects in the forced swim test in mice and showed significant anxiolytic activity in the plus-maze test in rats. The lead compound 36, a multi-receptor 5-HT(2A)/5-HT(7)/D(2)/D(3)/D(4) agent, also displayed significant antipsychotic properties in the MK-801-induced hyperlocomotor activity in mice.
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