title: Modification of the structure of 4, 6-disubstituted 2-(4-alkyl-1-piperazinyl)pyridines: synthesis and their 5-HT2A receptor activity.
abstract: Structure-activity relationship studies of a series of novel 4, 6-disubstituted 2-(1-piperazinyl)pyridines were conducted to revise our model of serotonin 5-HT(2A) receptor antagonist. Target compounds were synthesized using the benzotriazole-assisted Katritzky method. The majority of those compounds were found to be selective 5-HT(2A)/5-HT(1A) receptor ligands, though less potent than their previously described pyrimidine counterparts. In particular, the three compounds 6-8 showed the highest 5-HT(2A) receptor affinity (K(i) = 34-78 nM) and were classified as 5-HT(2A) antagonists in in vivo experiments. The influence of the structural modifications on the in vitro results was discussed; however, the elucidation of the role of the central core system requires further studies.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. paluchm@if-pan.krakow.pl
authors.forename: Maria H
authors.initials: MH
authors.lastname: Paluchowska
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Ryszard
authors.initials: R
authors.lastname: Bugno
authors.forename: Sijka
authors.initials: S
authors.lastname: Charakchieva-Minol
authors.forename: Anna
authors.initials: A
authors.lastname: Wesołowska
mesh_terms: D000818:Animals; D008024:Ligands; D008297:Male; D051379:Mice; D008954:Models, Biological; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010879:Piperazines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists