Latest Advances Towards the Discovery of 5-HT7 Receptor Ligands

Abstract

The 5-HT(7)receptor (5-HT(7)R), characterized in 1993, is the most recently described member of the serotonin family. Since its discovery, 5-HT(7)R has been the subject of extensive research due to its widespread distribution in the brain, suggestive of multiple central roles. The focus of this review is to illustrate the literature concerning developments of the last few years (2007-2010) towards the discovery of novel and selective 5-HT(7)R ligands, agonists, antagonist and inverse agonists.

Design and synthesis of new homo and hetero bis-piperazinyl-1-propanone derivatives as 5-HT7R selective ligands over 5-HT1AR

“…5,6 These serotonin receptor subtypes are co-expressed in major brain structures (limbic areas, hippocampus, and raphe nuclei), however they differ for the type of G protein, thus G i for 5-HT 1A R and G s for 5-HT 7 R. For that reason, they modulate the same second messenger systems even though in the opposite way and could be involved in an interesting functional cross-talk between them as it has been suggested. 7 The 5-HT 7 R is the last discovered member of serotonin receptors and our interest on this receptor is due to its involvement in diseases like anxiety, schizophrenia, and depression.…”

“…16 Consequently, the next step of the work was focused on the modification of the substituents at the piperazine, labeled as HYD/Ar 1 domain. The introduction of a 4-ClC 6 The introduction of a benzylamine in HYD/Ar 2 domain (compound 30) and concurrently in HYD/Ar 1 , and HYD/Ar 2 (compound 33) has significantly affected the binding to 5-HT 1A R and to 5-HT 7 R (13 vs 30 and 13 vs 33, Table 1). …”

Synthesis and Experimental Validation of New Designed Heterocyclic Compounds with Antiproliferative Activity versus Breast Cancer Cell Lines MCF-7 and MDA-MB-231

“…Among them, 167 were previously synthesized for other applications such as 1 adrenergic, 5-HT 1A serotonergic, or endothelin receptor ligands and antiproliferative compounds active in prostate tumor cell lines [15][16][17][18][19][20][21][22][23][24][25]. Moreover, 9 compounds were designed and synthesized based on the recent literature [26][27][28] reporting the activity of pyrimidinketones against MCF-7 cell line. The new compounds retain the same heterocyclic core with respect to the literature ones, modified by fusion with thiophene and pyrazole rings with different substituents.…”

Synthesis and binding properties of new long-chain 4-substituted piperazine derivatives as 5-HT1A and 5-HT7 receptor ligands

“…[1][2][3][4][5][6] Medicinal chemistry research had successfully obtained highaffinity and selective ligands for each of these receptors with the aim to clarify their role in the above mentioned physiological and pathological processes. [3][4][5] Recently, part of the research efforts have been directed towards the development of ligands for both receptors. Particularly, a number of studies suggest that ligands with partial agonist at 5-HT 1A R and antagonist properties on 5-HT 7 R can display antidepressant-like effects.…”

“…of pharmacological tools [3][4][5] and successfully developed drugs, such as buspirone, gepirone, tandospirone, and aripiprazole. 6,10 The drug potential of LCAPs had led to various SAR studies focused on the three main structural features of these agents ( Fig.…”