title: Synthesis and functional activity of (2-aryl-1-piperazinyl)-N-(3-methylphenyl)acetamides: selective dopamine D4 receptor agonists.
abstract: Diaryl piperazine acetamides were identified as potent and selective dopamine D(4) receptor agonists. Our strategy is based on an amide bond reversal of an acid sensitive, dopamine D(4) receptor partial agonist, PD 168077. This reversal provided compounds with excellent potency and improved stability. Systematic evaluation of the substitution on the aryl piperazine portion revealed a significant effect on functional activity. The synthesis and biological activity of these new dopamine D(4) agonists is discussed.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research, Abbott Laboratories, Abbott Park, IL 60064, USA. mark.a.matulenko@abbott.com
authors.forename: Mark A
authors.initials: MA
authors.lastname: Matulenko
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Hakeem
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*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D050638:Receptors, Dopamine D4
chemical_list: D000081:Acetamides; C493599:DRD4 protein, human; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D002118:Calcium