title: Synthesis and 5-HT1A/5-HT2A activity of some butyl analogs in the group of phenylpiperazine alkyl pyrimido[2,1-f]theophyllines.
abstract: New arylpiperazines with a four-methylene spacer containing a terminal pyrimido[2,1-f] theophylline fragment were synthesized, and their 5-HT1A and 5-HT2A receptor affinities were determined. All these compounds displayed a high affinity for 5-HT1A receptors (Ki=0.5-21.5 nM), and low affinity for 5-HT2A ones. The results of in vivo experiments showed that compounds revealed potential agonistic activity at presynaptic 5-HT1A receptors, whereas their functional activity at postsynaptic 5-HT1A sites was diversified. In fact, compounds and behaved like partial agonists, antagonists or agonists of postsynaptic 5-HT1A receptors, respectively. The pharmacological properties of the tested compounds were discussed in comparison with those of the three methylene-analogs described earlier.
authors.affiliation: Department of Pharmaceutical Chemistry, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kołaczkowski
authors.forename: Paweł
authors.initials: P
authors.lastname: Zajdel
authors.forename: Omeran
authors.initials: O
authors.lastname: Fhid
authors.forename: Beata
authors.initials: B
authors.lastname: Duszyńska
authors.forename: Ewa
authors.initials: E
authors.lastname: Tatarczyńska
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D001831:Body Temperature / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008024:Ligands; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D018490:Serotonin Agents; D044282:Receptor, Serotonin, 5-HT1A; D013806:Theophylline