Abstract
8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones have been identified as highly potent 5-HT(1A/B/D) receptor antagonists with and without additional SerT activity and a high degree of selectivity over hERG potassium channels. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.
MeSH terms
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Animals
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Benzoxazines / chemistry*
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Benzoxazines / metabolism
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Benzoxazines / pharmacology
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CHO Cells
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Cricetinae
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Cricetulus
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Piperazines / chemistry*
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Piperazines / metabolism
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Piperazines / pharmacology
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Rats
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Receptors, Serotonin, 5-HT1 / metabolism
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Selective Serotonin Reuptake Inhibitors / chemistry*
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Selective Serotonin Reuptake Inhibitors / metabolism
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Serotonin 5-HT1 Receptor Antagonists*
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Serotonin Antagonists / chemistry*
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Serotonin Antagonists / metabolism
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Serotonin Antagonists / pharmacology
Substances
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Benzoxazines
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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KCNH2 protein, human
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Piperazines
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Receptors, Serotonin, 5-HT1
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin Antagonists
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Serotonin Uptake Inhibitors