title: A search for new 5-HT1A/5-HT2A receptor ligands. In vitro and in vivo studies of 1-[omega-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-ones.
abstract: A series of 1-¿omega-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-one derivatives 2-14 was synthesized in order to obtain ligands with a dual 5-HT1A/5-HT2A activity. The majority of those compounds (2-5, 7, 10-13) exhibited a high 5-HT1A (Ki = 2-44 nM) and/or 5-HT2A affinity (Ki = 51 and 39 for 5 and 7, respectively). Induction of lower lip retraction (LLR) and behavioral syndrome and inhibition of these effects evoked by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were used for determination the agonistic and antagonistic activity, respectively, at 5-HT1A receptors. The 5-HT2A antagonistic activity was assessed by the blocking effect on the head twitches induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in mice. Two of the tested compounds, 1-¿3-[4-(3-chlorophenyl)-1-piperazinyl]propyl¿-6-fluoroindolin-2(1 H)-one (5) and 1-¿3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl¿indolin-2(1H)-one (7), demonstrated a high 5-HT1A/5-HT2A affinity and an in vivo antagonistic activity towards both receptor subtypes.
authors.affiliation: Department of Medicinal Chemistry, Polish Academy of Sciences, Kraków, Poland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mokrosz
authors.forename: B
authors.initials: B
authors.lastname: Duszyńska
authors.forename: S
authors.initials: S
authors.lastname: Misztal
authors.forename: A
authors.initials: A
authors.lastname: Kłodzińska
authors.forename: E
authors.initials: E
authors.lastname: Tatarczyńska
authors.forename: E
authors.initials: E
authors.lastname: Chojnacka-Wójcik
authors.forename: M
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D007211:Indoles; D008024:Ligands; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents