title: New imide 5-HT1A receptor ligands - modification of terminal fragment geometry.
abstract: Two sets of new o-methoxyphenylpiperazine (MPP; series a) and 1,2,3,4-tetrahydroisoquinoline (THIQ; series b) derivatives, containing various imide moieties derived from NAN190, were synthesized and evaluated in vitro for their ability to bind to the serotonin 5-HT(1A) and 5-HT(2A) receptors. All new derivatives from series a demonstrated high 5-HT(1A) affinities, whereas THIQ analogues were much less active. With respect to 5-HT(2A) receptors, three MPP derivatives presented moderate activity but the rest of the investigated compounds were practically inactive. The influence of changes in terminus geometry on 5-HT(1A) receptor affinity was analyzed in regard to model compounds NAN190and MM199.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacology of the Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. bojarski@if-pan.krakow.pl
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Mokrosz
authors.forename: Beata
authors.initials: B
authors.lastname: Duszyńska
authors.forename: Aneta
authors.initials: A
authors.lastname: Kozioł
authors.forename: Ryszard
authors.initials: R
authors.lastname: Bugno
mesh_terms: D000818:Animals; D002065:Buspirone / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C098652:8-(4-(2-(1,2,3,4-tetrahydroisoquinolinyl))butyl)-8-azaspiro(4.5)decane-7,9-dione; D008024:Ligands; D010879:Piperazines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D044005:Tetrahydroisoquinolines; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C040083:1-(2-methoxyphenyl)piperazine; D002065:Buspirone