The affinity of several antidepressant and antipsychotic drugs for 5-HT₇ receptor, along with their distribution in CNS, suggested their involvement in the physiopathology of brain disorders. Indeed, some recent studies demonstrated direct involvement of 5-HT₇ receptors in depression, anxiety and mood diseases [1-3].

To better characterize the 5-HT₇ receptor, a new potent and selective compounds are required. Different research centers (among others our Department) are engaged in modeling, design, synthesis and structure-activity relationships studies of new 5-HT₇ ligands.

Here we present a series of 2-(1-arylsulfonylpiperidyn-2-yl)ethyl derivatives with various changes of aromatic substituent in arylsulfonylpiperidine moiety and modifications in terminal amine fragment.

In the competition binding studies of the investigated compounds, both selective 5-HT₇ receptor ligands and that with mixed 5-HT_2A/5-HT₇/D₂ pharmacological profile were found. The structure-affinity relationships for all the new derivatives are discussed.

This study was partly supported by the Ministry of Science and Higher Education (MNiSW), Grant No. N405 026 32/1743

References

[1] Guscott M., Bristow L. J , Hadingham K , Rosahl T. W , Beer M. S., Stanton J. A., Bromidge F., Owens A. P., Huscroft I., Myers J., Rupniak N. M., Patel S., Whiting P. J., Hutson P. H.,Fone K. C., Biello S. M., Kulagowski J. J., McAllister G. Neuropharmacology. 2005, 48(4), 492-502.
[2] Wesołowska A., Tatarczyńska E., Nikiforuk A., Chojnacka-Wójcik E. Eur. J. Pharmacol. 2007, 555(1),43-7.
[3] Hedlund P. B., Sutcliffe J. G. Neurosci. Lett. 2007, 414(3), 247-51.

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