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Clozapine derived 2,3-dihydro-1H-1,4- and 1,5-benzodiazepines with D4 receptor selectivity: synthesis and biological
Thomas Hussenether1, Harald Hübner, Peter Gmeiner
1Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
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.
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