title: N-(4-(4-(2-Halogenophenyl)piperazin-1-yl)butyl) substituted cinnamoyl amide derivatives as dopamine D2 and D3 receptor ligands.
abstract: A series of eight substituted N-(4-(4-(2-halogenophenyl)piperazin-1-yl)butyl)-3-phenylacryl amide derivatives have been synthesized and screened for binding affinities at dopamine hD(2) and hD(3) receptors. All compounds have shown high to remarkable receptor affinities and some have led to distinct selectivity for D(3) receptors. Highest D(3)-receptor affinity has been observed for 3-(4-aminophenyl)-N-(4-(4-(2-fluorophenyl)piperazin-1-yl)butyl)acryl amide (hD(3) K(i) 0.9 nM; hD(2) K(i) 17.4 nM). Selectivity ratio has been best for 3-(4-chlorophenyl)-N-(4-(4-(2-fluorophenyl)piperazin-1-yl)butyl)acryl amide with a 56-fold preference for hD(3) versus hD(2). A functional activity test has been performed by a mitogenesis test for N-(4-(4-(2-fluorophenyl)piperazin-1-yl)butyl)-3,3-diphenylacryl amide, which, surprisingly, has shown full agonist properties.
authors.affiliation: Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Saur
authors.forename: Anneke E
authors.initials: AE
authors.lastname: Hackling
authors.forename: Sylvie
authors.initials: S
authors.lastname: Perachon
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Schwartz
authors.forename: Pierre
authors.initials: P
authors.lastname: Sokoloff
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
mesh_terms: D000478:Alkylation; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3 / Q000187:drug effects*
chemical_list: D006846:Hydrocarbons, Halogenated; D007202:Indicators and Reagents; D008024:Ligands; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3