Employing the D(4) 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 D(2) family. Subtype selectivity for D(4) 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.

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

SANNA, FABRIZIO
Primo
;
2013-01-01

Abstract

Employing the D(4) 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 D(2) family. Subtype selectivity for D(4) 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.
2013
GPCR; Dopamine; Subtype selectivity; Ligand efficacy; Paracyclophane; Planar chirality
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/76724
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