Abstract
A series of pyrrolo-benzo-1,4-diazine analogs have been synthesized and displayed potent Nav1.7 inhibitory activity and moderate selectivity over Nav1.5. The syntheses, structure-activity relationships, and selected pharmacokinetic data of these analogs are described. Compound 41 displayed anti-nociceptive efficacy in the rat CFA pain model at 100 mpk oral dosing.
Keywords:
Nav1.5; Nav1.7; Pain; Pyrrolo-benzo-1,4-diazine; Sodium channel blockers.
Copyright © 2014 Elsevier Ltd. All rights reserved.
MeSH terms
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Dose-Response Relationship, Drug
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Drug Discovery*
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Humans
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Molecular Structure
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NAV1.7 Voltage-Gated Sodium Channel / metabolism*
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Quinoxalines / chemical synthesis
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Quinoxalines / chemistry
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Quinoxalines / pharmacology*
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Sodium Channel Blockers / chemical synthesis
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Sodium Channel Blockers / chemistry
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Sodium Channel Blockers / pharmacology*
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Spiro Compounds / chemical synthesis
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology*
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Structure-Activity Relationship
Substances
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NAV1.7 Voltage-Gated Sodium Channel
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Quinoxalines
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Sodium Channel Blockers
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Spiro Compounds