Discovery of dopamine D(4) receptor antagonists with planar chirality.

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Sanna F, Ortner B, Hubner H, Lober S, Tschammer N, Gmeiner P

Discovery of dopamine D(4) receptor antagonists with planar chirality.

Bioorg Med Chem. 2013 Apr 1;21(7):1680-4. doi: 10.1016/j.bmc.2013.01.065. Epub 2013 Feb 5.

PubMed ID

23428965 [ View in PubMed

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Abstract

Employing the D4 selective phenylpiperazine 2 as a lead compound, planar chiral analogs with paracyclophane substructure were synthesized and evaluated for their ability to bind and activate dopamine receptors. The study revealed that the introduction of a [2.2]paracyclophane moiety is tolerated by dopamine receptors of the D2 family. Subtype selectivity for D4 and ligand efficacy depend on the absolute configuration of the test compounds. Whereas the achiral single-layered lead 2 and the double-layered paracyclophane (R)-3 showed partial agonist properties, the enantiomer (S)-3 behaved as a neutral antagonist.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Dopamine	Dopamine D2 receptor	Ki (nM)	110	N/A	N/A	Details
Dopamine	Dopamine D2 receptor	Ki (nM)	190	N/A	N/A	Details
Dopamine	Dopamine D3 receptor	Ki (nM)	21	N/A	N/A	Details