Abstract
We have synthesized and biologically evaluated 1,4-diazepane derivatives as T-type calcium channel blockers. In this study, we discovered compound 4s, a potential T-type calcium channel blocker with good selectivity over hERG and N-type calcium channels. In addition, it exhibited favorable pharmacokinetic characteristics for further investigation of T-type calcium channel related diseases.
2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Antihypertensive Agents / chemical synthesis
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Antihypertensive Agents / chemistry*
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Antihypertensive Agents / pharmacokinetics
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Azepines / chemical synthesis*
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Azepines / chemistry
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Azepines / pharmacokinetics
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacokinetics
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Calcium Channel Blockers / chemical synthesis*
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Calcium Channel Blockers / chemistry
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Calcium Channel Blockers / pharmacokinetics
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Calcium Channels, T-Type / chemistry*
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Calcium Channels, T-Type / metabolism
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Cell Line
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Humans
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Rats
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Trans-Activators / metabolism
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Transcriptional Regulator ERG
Substances
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1,4-diazepane
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Antihypertensive Agents
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Azepines
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Benzimidazoles
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Calcium Channel Blockers
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Calcium Channels, T-Type
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ERG protein, human
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Trans-Activators
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Transcriptional Regulator ERG