Clozapine derived 2,3-dihydro-1H-1,4- and 1,5-benzodiazepines with D4 receptor selectivity: synthesis and biological testing.

Thomas Hussenether, Harald Hübner, Peter Gmeiner, Reinhard Troschütz

Index: Bioorg. Med. Chem. 12(10) , 2625-37, (2004)

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Abstract

Novel 4-arylpiperazin-1-yl-substituted 2,3-dihydro-1H-1,4- and 1H-1,5-benzodiazepines and their aza-analogues were synthesized as debenzoclozapine derivatives for evaluation as potential D4-ligands. While Ki values of some of the title compounds came within the range of clozapine, they showed an impressively greater selectivity over other dopamine receptor subtypes, especially D2. For the most promising compounds, intrinsic activity and binding properties to serotonin 5-HT1A and 5-HT2 were also determined.