title: 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.
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.
authors.affiliation: Department of Medical Chemistry, The Medical University of Warszawa, Oczki 3, PL 02-007 Warszawa, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kossakowski
authors.forename: Aldona
authors.initials: A
authors.lastname: Raszkiewicz
authors.forename: Ryszard
authors.initials: R
authors.lastname: Bugno
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
mesh_terms: D007094:Imides / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007094:Imides; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D044282:Receptor, Serotonin, 5-HT1A