The role of the 5-HT₇ receptors in the CNS and the periphery has not been fully clarified since to date there are only limited number of the selective-active ligands. During screening of our compounds library against the 5-HT₇ receptor from rat hypothalamic membranes, it was found that a lot of agents, besides 5-HT_1A and/or 5-HT_2A receptors activity, displayed also a significant affinity towards 5-HT₇ sites. The 4-mono, and 4,6-disubstituted 2-(1-piperazinyl)pyridines were particularly interesting, since compounds of such structure have never been reported as 5-HT₇ receptor ligands.

Here we report the 5-HT₇ receptor affinity for some previously described 4,6-disubstituted 2-(1-piperazinyl)pyridines as well as a series of newly designed and synthesized analogues. The target compounds were synthesized using the benzotriazole-assisted Katritzky method. The affinity for three serotoninergic receptor subtypes (5-HT_1A, 5-HT_2A and 5-HT₇) were determined and some structure-affinity relationships are discussed.

In addition, an automated docking to homology model of 5-HT₇ receptor was performed, and it was found that in the best PMF-scored complexes ligands were placed between helices 2, 3 and 7, revealing a strong interaction formed by heteroatom and indole nitrogen of Trp7.40.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/6590 must be provided.

1. Induced Fit Homology Model of the 5-HT₆ Serotonin Receptor - Application for Virtual Screening
2. Examination of 5-HT₆ receptor affinity in the group of arylsulfonamide derivatives
3. Synthesis of long-chain arylpiperazine theophylline derivatives as potential 5-HT₇ and 5-HT₆ receptors ligands
4. Searching for the 5-HT₇ receptor ligands in the series of new 1,2,3,4-tetrahydroisoquinolines with imide fragment
5. Synthesis and molecular modeling of 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides as potential 5-HT₇ receptor ligands
6. Mannich bases, 5-arylimidazolidine-2,4-dione derivatives with arylpiperazine moiety, as 5-HT_1A receptor ligands with serotonin transporter affinity
7. Homology modeling of the 5-HT_1A and 5-HT_2A serotonin receptors on the novel ß₂-adrenergic receptor template
8. 2-(1-Arylsulfonylpiperidin-2-yl)ethyl derivatives as 5-HT₇ receptor ligands: synthesis and their affinity for 5-HT_1A/5-HT_2A/5-HT₇/D₂ receptors
9. SAR studies of novel 5-HT₇R ligands with different spacers between aryl and amine moieties
10. STRUCTURAL MODIFICATIONS OF SOME ARYLPIPERAZINE LIGANDS TOWARDS IMPROVED SELECTIVITY FOR 5-HT₇ RECEPTORS
11. THE BIOLOGICAL TARGET DERIVED PHARMACOPHORIC MODEL FOR 5-HT₇ SEROTONIN RECEPTOR ANTAGONISM
12. 8-ALKOXY-PURINE-2,6-DIONES WITH 7-PHENYLPIPERAZINYLALKYL AND 7-TETRAHYDRO-ISOQUINOLINYLALKYL MOIETIES AS 5-HT_1A, 5-HT_2A, 5-HT₇ RECEPTOR LIGANDS
13. DESIGN AND SYNTHESIS OF NEW 7-PHENYLPIPERAZINYLALKYL AND 7-TETRAHYDROISOQUINOLINYLALKYL DERIVATIVES OF PURINE-2,6,8-TRIONE AS POTENTIAL SEROTONIN RECEPTOR AGENTS