Synthesis and characterization of selective dopamine D(2) receptor ligands using aripiprazole as the lead compound.

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Vangveravong S, Zhang Z, Taylor M, Bearden M, Xu J, Cui J, Wang W, Luedtke RR, Mach RH

Synthesis and characterization of selective dopamine D(2) receptor ligands using aripiprazole as the lead compound.

Bioorg Med Chem. 2011 Jun 1;19(11):3502-11. doi: 10.1016/j.bmc.2011.04.021. Epub 2011 Apr 16.

PubMed ID

21536445 [ View in PubMed

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Abstract

A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D((2)-like) dopamine receptors. These compounds also share structural elements with the classical D((2)-like) dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H )-one oxalate (7) were found to (a) bind to the D(2) receptor subtype with high affinity (K(i) values < 0.3 nM), (b) exhibit >50-fold D(2) versus D(3) receptor binding selectivity and (c) be partial agonists at both the D(2) and D(3) receptor subtype.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Aripiprazole	Dopamine D2 receptor	Ki (nM)	3.1	N/A	N/A	Details
Aripiprazole	Dopamine D3 receptor	Ki (nM)	6.8	N/A	N/A	Details
Aripiprazole	Dopamine D4 receptor	Ki (nM)	168	N/A	N/A	Details