title: Synthesis and activity of 2-[4-(4-[3H]-2-cyanophenyl)piperazinyl]-N-(2,4,6-[3H]3-3-methylphenyl)acetamide: a selective dopamine D4 receptor agonist and radioligand.
abstract: The first selective dopamine D4 agonist radioligand is described. The synthesis of these piperazine radioligands relied on the transformation of brominated precursors 4a and 4b with tritium gas in the presence of a sensitive cyano functional group. The specific activity of these two radioligands was measured and [3H]6b found to be suitable for use in D4 saturation and competition binding studies. The synthesis, biological, and radioactivity of this new agonist radioligand as well as preliminary SAR will be discussed.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A/L16, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. mark.a.matulenko@abbott.com
authors.forename: Mark A
authors.initials: MA
authors.lastname: Matulenko
authors.forename: Bruce
authors.initials: B
authors.lastname: Surber
authors.forename: Leimin
authors.initials: L
authors.lastname: Fan
authors.forename: Teodozyi
authors.initials: T
authors.lastname: Kolasa
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakane
authors.forename: Marc A
authors.initials: MA
authors.lastname: Terranova
authors.forename: Marie E
authors.initials: ME
authors.lastname: Uchic
authors.forename: Loan N
authors.initials: LN
authors.lastname: Miller
authors.forename: Renjie
authors.initials: R
authors.lastname: Chang
authors.forename: Diana L
authors.initials: DL
authors.lastname: Donnelly-Roberts
authors.forename: Marian T
authors.initials: MT
authors.lastname: Namovic
authors.forename: Robert B
authors.initials: RB
authors.lastname: Moreland
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Brioni
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Stewart
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D013329:Structure-Activity Relationship; D014316:Tritium
chemical_list: D000081:Acetamides; C493599:DRD4 protein, human; D008024:Ligands; D010879:Piperazines; D017448:Receptors, Dopamine D2; D014316:Tritium; D050638:Receptors, Dopamine D4