Continuing study of the influence of linker conformation in the structure of long-chain arylpiperazines on the affinity to serotonin 5-HT_1A and 5-HT₇ receptors [1], new flexible and partly constrained derivatives were synthesized. Well characterized, potent 5-HT_1A agents (i.e. NAN-190 and PK 13) were selected as a parent molecules and two series of compounds containing o-metoxyphenylpiperazine or 1,2,3,4-tetrahydroizoquinoline pharmacophores were investigated. Structural modifications involved: elongation of polymethylene chain to five and six carbon atoms and introduction of m-xylene and p-xylene moieties into linker fragment. Results of in vitro binding experiments for 5-HT_1A and 5-HT₇ receptors are compared to that obtained for previously published analogues with tetrametylene linkers.

This study was partly supported by the Ministry of Science and Higher Education (MNiSW), Grant No. 2 P05F 019 30

[1] Bojarski,A.J.; Duszyńska,B.; Kołaczkowski,M.; Kowalski,P.; Kowalska,T. The impact of spacer structure on 5-HT₇ and 5-HT_1A receptor affinity in the group of long-chain arylpiperazine ligands. Bioorg.Med.Chem.Lett. 2004, 14, 5863-6.

• 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/14796 must be provided.

1. Examination of 5-HT₆ receptor affinity in the group of arylsulfonamide derivatives
2. Quinolinesulfonamides as potential 5-HT₇ and 5-HT_1A receptor ligands
3. Synthesis of long-chain arylpiperazine theophylline derivatives as potential 5-HT₇ and 5-HT₆ receptors ligands
4. Searching for lead molecules as potential new CNS agents in the serotonin 5-HT₆ screening assay
5. Solid-phase synthesis and preliminary biological investigation of arylpiperazine library as 5-HT_1A and 5-HT_2A receptor ligands
6. New serotonin receptors ligands in the group of 8-acylamide derivatives of 1,3-dimethyl-7-[(4-phenyl- piperazin-1-yl)-alkyl]-1H-purine-2,6-(3H,7H)-dione
7. Synthesis and serotonin receptors activity of new purine-2,6-dione derivatives with arylpiperazinylalkoxy moieties
8. NEW DUAL 5-HT₇/5-HT_1A LIGANDS WITH ANTIDEPRESSANT AND ANXIOLYTIC-LIKE ACTIVITY
9. 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
10. DESIGN AND SYNTHESIS OF NEW 7-PHENYLPIPERAZINYLALKYL AND 7-TETRAHYDROISOQUINOLINYLALKYL DERIVATIVES OF PURINE-2,6,8-TRIONE AS POTENTIAL SEROTONIN RECEPTOR AGENTS