title: Discovery of dopamine D₄ receptor antagonists with planar chirality.
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.
authors: Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
authors: Fabrizio
authors: F
authors: Sanna
authors: Birgit
authors: B
authors: Ortner
authors: Harald
authors: H
authors: Hübner
authors: Stefan
authors: S
authors: Löber
authors: Nuska
authors: N
authors: Tschammer
authors: Peter
authors: P
authors: Gmeiner
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018492:Dopamine Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D050638:Receptors, Dopamine D4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D018492:Dopamine Antagonists; D010879:Piperazines; D050638:Receptors, Dopamine D4; C031503:phenylpiperazine