title: Effect of the amide fragment on 5-HT1A receptor activity of some analogs of MP 3022.
abstract: A new set (3-11) of analogs of MP 3022 (1) containing the amide bond inserted into the intermediate chain linking the terminal heteroaromatic and 1-(2-methoxyphenyl)piperazine moieties were prepared and their 5-HT1A and 5-HT2A receptor affinities were determined. Only compounds with trimethylene chain between amide and arylpiperazine fragments (5a, 5b, 7a, 7b and 11) showed satisfactory affinity for 5-HT1A receptor (Ki = 42-87 nM) and high 5-HT2A/5-HT1A selectivity. The new 5-HT1A receptor ligands were investigated in vivo to determine their 5-HT1A agonistic or antagonistic properties. Compounds 7a and 7b with terminal indazole fragment as well as 11 with phenyl substituent behaved like weak 5-HT1A receptor antagonists. The structure-affinity relationship studies in this series of compounds revealed that the amide group along with the terminal aromatic fragments contributed to interaction with 5-HT1A receptor sites, whereas in vivo results indicated that introduction of the amide group into presented arylpiperazine structures was not a profitable modification for their 5-HT1A functional activity.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
authors.forename: M H
authors.initials: MH
authors.lastname: Paluchowska
authors.forename: S
authors.initials: S
authors.lastname: Charakchieva-Minol
authors.forename: E
authors.initials: E
authors.lastname: Tatarczyńska
authors.forename: A
authors.initials: A
authors.lastname: Kłodzińska
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000577:Amides; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D014230:Triazoles; C088974:4-(3-(benzotriazol-1-yl)propyl)-1-(2-methoxyphenyl)piperazine