Synthesis and functional activity of (2-aryl-1-piperazinyl)-N-(3-methylphenyl)acetamides: selective dopamine D4 receptor agonists.
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.
Matulenko
Mark A
MA
Neuroscience Research, Global Pharmaceutical Research, Abbott Laboratories, Abbott Park, IL 60064, USA. mark.a.matulenko@abbott.com
Hakeem
Ahmed A
AA
Kolasa
Teodozyi
T
Nakane
Masaki
M
Terranova
Marc A
MA
Uchic
Marie E
ME
Miller
Loan N
LN
Chang
Renjie
R
Donnelly-Roberts
Diana L
DL
Namovic
Marian T
MT
Moreland
Robert B
RB
Brioni
Jorge D
JD
Stewart
Andrew O
AO
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
D000081:Acetamides; C493599:DRD4 protein, human; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D002118:Calcium