title: Synthesis and receptor binding assay of indolin-2-one derivatives as dopamine D4 receptor ligands.
abstract: Five indolin-2-one derivatives bearing piperazinylbutyl side chains attached to the amide nitrogen were synthesized from 2-indolinone. 1-(4-Bromobutyl)-indolin-2-one was reacted with 1-piperazinecarboxaldehyde to form 1-(4-(4-formyl-1-piperazinyl)butyl)indolin-2-one (2). In the presence of H2SO4, the aldehyde moiety was removed from 1-(4-(4-formyl-1-piperazinyl)butyl)indolin-2-one and then 1-(4-(1-piperazinyl)butyl)indolin-2-one (3) was obtained, this compound was reacted with benzaldehyde derivatives to give the target compounds 4 a-e by N-alkylation reaction. The structures of the intermediates and the target compounds were characterized by 1H NMR, ESI-MS spectra and elemental analyses. In vitro receptor binding assays at D2, D3, D4 receptor subtypes of the target compounds were performed and the five compounds showed selectivity towards D2-like receptors. Among them, 1-(4-(4-(4-hydroxybenzy)-1-piperazinyl)butyl) indolin-2-one (4c) exhibited a remarkable affinity and selectivity to D4 receptor with K(i) value of 0.5 nM. The results indicated that 1-(4-(4-(4-hydroxybenzy)-1-piperazinyl)butyl)indolin-2-one might be a potential dopamine D4 receptor ligand.
authors.forename: Gu-cai
authors.initials: GC
authors.lastname: Li
authors.forename: Bian-ling
authors.initials: BL
authors.lastname: Zhang
authors.forename: Jiao-yun
authors.initials: JY
authors.lastname: Xia
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Fang
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D050638:Receptors, Dopamine D4 / Q000187:drug effects* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D007211:Indoles; D008024:Ligands; C456900:indolin-2-one; D050638:Receptors, Dopamine D4