Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626.

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Vangveravong S, Taylor M, Xu J, Cui J, Calvin W, Babic S, Luedtke RR, Mach RH

Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626.

Bioorg Med Chem. 2010 Jul 15;18(14):5291-300. doi: 10.1016/j.bmc.2010.05.052. Epub 2010 May 24.

PubMed ID

20542439 [ View in PubMed

]

Abstract

A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds share structural elements with the classical D2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4-(4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (6) and 4-(4-iodophenyl)-1-((5-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D2 versus D3 receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D2 binding affinity and the D2 versus D3 selectivity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Haloperidol	Dopamine D2 receptor	Ki (nM)	1.1	N/A	N/A	Details
Haloperidol	Dopamine D3 receptor	Ki (nM)	12.7	N/A	N/A	Details