Design, synthesis, and evaluation of potent and selective ligands for the dopamine 3 (D3) receptor with a novel in vivo behavioral profile.
A series of compounds structurally related to pramipexole were designed, synthesized, and evaluated as ligands for the dopamine 3 (D3) receptor. Compound 12 has a K(i) value of 0.41 nM to D3 and a selectivity of >30000- and 800-fold over the D1-like and D2 receptors, respectively. Our in vivo functional assays showed that this compound is a partial agonist at the D3 receptor with no detectable activity at the D2 receptor.
Chen
Jianyong
J
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Collins
Gregory T
GT
Zhang
Jian
J
Yang
Chao-Yie
CY
Levant
Beth
B
Woods
James
J
Wang
Shaomeng
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007035:Hypothermia / Q000139:chemically induced; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D000077487:Pramipexole; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D012680:Sensitivity and Specificity; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015000:Yawning / Q000187:drug effects
D052160:Benzothiazoles; D018491:Dopamine Agonists; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000077487:Pramipexole
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