Since the discovery of the 5-HT₇ receptors and their potential therapeutic applications the search for potent and selective ligands has been initiated. More than 10 years of investigations resulted in finding a few selective antagonists like SB-269970-A and SB-656104-A. Several research groups and some pharmaceutical companies are active in this field, and a number of papers describing structure-activity relationship (SAR) [1] as well as some pharmacophoric models [2] have been published.

As a part of our research program directed towards the design and synthesis of potent and selective 5-HT₇ ligands we obtained new series of compounds with flexible and partly constrained spacer between aryl and amine fragment. Radioligand binding study showed that the investigated compounds reveal diverse affinity for 5-HT₇ receptor and selectivity over 5-HT_1A/5-HT_2A/D₂ sites. 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] Leopoldo M.Curr. Med. Chem. 2004, 11(5), 629–661.
[2] Bojarski A. J. Curr. Top. Med. Chem. 2006, 6(18), 2005–26.

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