Introduction of a new complex imide system into the structure of LCAPs. The synthesis and a 5-HT1A, 5-HT2A and D2 receptor binding study

Jerzy Kossakowski; Aldona Raszkiewicz; Ryszard Bugno; Andrzej J Bojarski

Introduction of a new complex imide system into the structure of LCAPs. The synthesis and a 5-HT1A, 5-HT2A and D2 receptor binding study

Pol J Pharmacol. 2004 Nov-Dec;56(6):843-8.

Authors

Jerzy Kossakowski¹, Aldona Raszkiewicz, Ryszard Bugno, Andrzej J Bojarski

Affiliation

¹ Department of Medical Chemistry, The Medical University of Warszawa, Oczki 3, PL 02-007 Warszawa, Poland.

PMID: 15662099

Abstract

A series of 17 long-chain arylpiperazines containing bulky, complex imide systems (5,8-dimethyl-3b,9-epoxy-(3a,4,5,6,7,8,9,9a)-octahydro-1H-benzo[e]isoindole-1,3(2H)-dione or 4,9-diphenyl-4,9-epoxy-3a,4,9,9a-tetra-hydro-1H-benzo[f]isoindole-1,3(2H)-dione) was synthesized and evaluated for their affinity for serotonin 5-HT1A, 5-HT2A and dopamine D2 receptors. Most of the new compounds showed moderate activity at 5-HT1A binding sites (Ki = 100-492 nM), and two derivatives were found to have marked affinity for the 5-HT2A receptor subtype. None of the tested compounds displayed appreciable binding to dopamine D2 receptors Structure-activity relationships were discussed in respect to an arylpiperazine fragment, whereas the comparison of different imide terminals enabled determination of the size of a hydrophobic pocket (approximately 300 A3) within the 5-HT1A receptor.

MeSH terms

Imides / chemistry*
Imides / metabolism
Molecular Structure
Piperazines / chemistry*
Piperazines / metabolism
Protein Binding
Receptor, Serotonin, 5-HT1A / chemistry
Receptor, Serotonin, 5-HT1A / metabolism*
Receptor, Serotonin, 5-HT2A / chemistry
Receptor, Serotonin, 5-HT2A / metabolism*
Receptors, Dopamine D2 / chemistry
Receptors, Dopamine D2 / metabolism*

Substances

Imides
Piperazines
Receptor, Serotonin, 5-HT2A
Receptors, Dopamine D2
Receptor, Serotonin, 5-HT1A