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 stabilit...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2004-07, Vol.12 (13), p.3471-3483
Main Authors: MATULENKO, Mark A, HAKEEM, Ahmed A, MORELAND, Robert B, BRIONI, Jorge D, STEWART, Andrew O, KOLASA, Teodozyi, NAKANE, Masaki, TERRANOVA, Marc A, UCHIC, Marie E, MILLER, Loan N, CHANG, Renjie, DONNELLY-ROBERTS, Diana L, NAMOVIC, Marian T
Format: Article
Language:English
Subjects:
Acetamides - chemical synthesis
Acetamides - chemistry
Acetamides - pharmacology
Biological and medical sciences
Calcium - metabolism
Catecholaminergic system
Cell Line
Dopamine Agonists - chemical synthesis
Dopamine Agonists - chemistry
Dopamine Agonists - pharmacology
Humans
Medical sciences
Molecular Structure
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Radioligand Assay
Receptors, Dopamine D2 - agonists
Receptors, Dopamine D2 - metabolism
Receptors, Dopamine D4
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Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(04)00337-2