title: Structure-5-HT/D2Receptor Affinity Relationship in a New Group of 1-Arylpiperazynylalkyl Derivatives of 8-Dialkylamino-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione.
abstract: In our previous papers, we have reported that some 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives possessed high affinity and displayed agonistic, partial agonistic, or antagonistic activity for serotonin 5-HT1Aand dopamine D2receptors. In order to examine further the influence of the substituent in the position 8 of the purine moiety and the influence of the xanthine core on the affinity for serotonin 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, and dopamine D2receptors, two series of 1-arylpiperazynylalkyl derivatives of 8-amino-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione were synthesized. All the final compounds were investigated in in vitro competition binding experiments for the serotonin 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, and dopamine D2receptors. The structure-affinity relationships for this group of compounds were discussed. For selected compounds, the functional assays for the 5-HT1Aand D2receptors were carried out. The results of the assays indicated that these groups of derivatives possessed antagonistic activity for 5-HT1Areceptors and agonistic, partial agonistic, or antagonistic activity for D2receptors. In total, 26 new compounds were synthesized, 20 of which were tested in in vitro binding experiments and 5 were tested in in vitro functional assays.
authors: Department of Medicinal Chemistry, Jagiellonian University Medical College, Kraków, Poland. zmudzki.p@gmail.com.
authors: Paweł
authors: P
authors: Żmudzki
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors: Grzegorz
authors: G
authors: Satała
authors: Department of Medicinal Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors: Grażyna
authors: G
authors: Chłoń-Rzepa
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors: Andrzej J
authors: AJ
authors: Bojarski
authors: Department of Pharmacological Screening, Jagiellonian University Medical College, Kraków, Poland.
authors: Grzegorz
authors: G
authors: Kazek
authors: Department of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland.
authors: Agata
authors: A
authors: Siwek
authors: Department of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland.
authors: Anna
authors: A
authors: Gryboś
authors: Department of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland.
authors: Monika
authors: M
authors: Głuch-Lutwin
authors: Department of Clinical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Anna
authors: A
authors: Wesołowska
authors: Department of Medicinal Chemistry, Jagiellonian University Medical College, Kraków, Poland.
authors: Maciej
authors: M
authors: Pawłowski
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D065127:Dopamine D2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D011687:Purines / Q000737:chemistry* / Q000494:pharmacology*; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D011687:Purines; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D000262:Adenylyl Cyclases; D002118:Calcium
keywords: 5-HT1A; D2; LCAPs; Theobromine