title: Structure-5-HT receptor affinity relationship in a new group of 7-arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione.
abstract: In our previous paper, we have reported that some 8-alkoxy-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives possessed high affinity and displayed agonistic activity for the serotonin 5-HT1A receptor. In order to examine the influence of the substituent in the position 8 of the purine moiety on the affinity for the serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors, a series of 7-arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl (THIQ) derivatives of 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione were synthesized. All the final compounds were investigated in in vitro competition binding experiments for serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors. The structure-affinity relationships for this group of compounds were discussed. For selected compounds, functional assays for the 5-HT1A receptor were carried out. The results of the assays indicated that these groups of derivatives possessed antagonistic activity for this receptor.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Żmudzki
authors.forename: Grażyna
authors.initials: G
authors.lastname: Chłoń-Rzepa
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kazek
authors.forename: Barbara
authors.initials: B
authors.lastname: Mordyl
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding; D011687:Purines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011687:Purines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D058829:Serotonin 5-HT1 Receptor Antagonists; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-HT1A; 5-HT2A; 5-HT7; LCAPs; Theophylline