Abstract
A series of novel 1,2,3-benzotriazin-4-one derivatives was prepared and evaluated as ligands for 5-HT receptors. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT1A receptor, some of which were selective with respect 5-HT2A and 5-HT2C receptors. Six analogues (1a, 2a, 2b, 2c, 2e and 2i) were selected and further evaluated for their binding affinities on D1, D2 dopaminergic and alpha1-, alpha2-adrenergic receptors. A o-OCH3 derivative (2e) bound at 5-HT1A sites with subnanomolar affinity (IC50 = 0.059 nM) and shows high selectivity over all considered receptors and may offer a new lead for the development of therapeutically efficacious agents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / ultrastructure
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Cell Membrane / chemistry
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Inhibitory Concentration 50
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Ligands
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Piperazines / chemical synthesis
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Piperazines / chemistry*
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Piperazines / metabolism
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Radioligand Assay
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Rats
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2C
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Receptors, Adrenergic / metabolism
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Receptors, Dopamine D1 / metabolism
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Receptors, Dopamine D2 / metabolism
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Receptors, Serotonin / metabolism*
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Receptors, Serotonin, 5-HT1
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Triazines / chemical synthesis
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Triazines / chemistry*
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Triazines / metabolism
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Visual Cortex / chemistry
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Visual Cortex / ultrastructure
Substances
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Ligands
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Piperazines
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2C
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Receptors, Adrenergic
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT1
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Triazines
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1,2,3-benzotriazin-4-one