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.
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.
Matulenko
Mark A
MA
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
Surber
Bruce
B
Fan
Leimin
L
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; 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
D000081:Acetamides; C493599:DRD4 protein, human; D008024:Ligands; D010879:Piperazines; D017448:Receptors, Dopamine D2; D014316:Tritium; D050638:Receptors, Dopamine D4