Long-chain arylpiperazines (LCAPs) with an amide or imide moiety represent one of the most important classes of 5-HT_1A receptor ligands (e.g. buspirone, tandospirone, WAY 100135, WAY 100635, NAN-190, flesinoxan). Buspirone, an arylpiperazine derivative with high 5-HT_1A receptor affinity, was the first agent in this class to be approved for clinical use. Most of the ligands with high affinity for the 5-HT_1A receptor exhibit a high level of undesired affinity for the α₁-adrenergic receptor [1].
The aim of the present study was to synthesize new ligands with higher affinity and selectivity to 5-HT_1A receptor. In this study buspirone was the key structure to which certain modifications were made, namely by introducing the imidazo[1,5-a]quinoline-1,3-dione residue. Other modifications were made by introducing different substituents at the piperazine ring nitrogen [2-7].
Multi-stage preparations were used to obtain 4,5-dihydro-3aH-imidazo[1,5-a]quinoline-1,3-dione, being the starting compound for further modification. N-alkilation of the imide group in 4,5-dihydro-3aH-imidazo[1,5-a]quinoline-1,3-dione followed, using 1,4-dibromobutane to yield monobromobuthyl derivative.
New targets were obtained by condensation of appropriate arylpiperazine with the above described monobutyl derivative.
The structure of the new compounds has been determined on the basis of spectra
(¹H and ¹³C NMR, IR) and elemental analysis.
The new compounds will be submitted to screening test to elucidate their affinity for
5-HT_1A receptor.

Ar = phenyl, 2-pyridyl, 2-pyrimidinyl, 2-fluorophenyl, 2-tolyl, 2-chlorophenyl, 2-methoxyphenyl, 3-fluormethylphenyl

[1] Trumpp-Kallmeyer S. et al.; J. Med. Chem. 35, 3448 (1992)
[2] Kuipers W. et al.; J. Med. Chem. 40, 300 (1997)
[3] Lopez-Rodriguez M. L.; J. Med. Chem. 42, 36 (1999)
[4] Abou-Gharbia M. A.; J. Med. Chem. 42, 5077 (1999)
[5] Herold F. et al.; Farmaco 57, 959 (2002)
[6] Herold F. et al.; Pharmazie 59, 99 (2004)
[7] Herold F. et al.; Eur. J. Med. Chem. in press 2006

• 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/6509 must be provided.

1. Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT_1A activity. Part 1.
2. Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT_1A activity. Part 2.
3. Synthesis of novel pyrido[1,2-c]pyrimidine derivatives as selective ligands for 5-HT_1A receptors
4. NEW PERHYDRO-PYRROLO[1,2-a]PYRAZINE DERIVATIVES WITH AN ARYLPIPERAZINE MOIETY AS LIGANDS FOR 5-HT_1A RECEPTOR.
5. NOVEL 4-ARYL-2H-PYRIDO[1,2-c]PYRIMI- DINES WITH 5-HT-TRANSPORTER AND 5-HT_1A AFFINITY
6. SYNTHESIS OF 8-FURFURYLTROPANE BENZAMIDE DERIVATIVES WITH POTENTIAL ANTIPSYCHOTIC ACTIVITY