Abstract
A novel series of cyanoguanidine-piperazine P2X(7) antagonists were identified and structure-activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X(7) receptors in addition to their ability to inhibit IL-1 beta release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 microM) in this latter assay and demonstrates moderate clearance in-vivo.
MeSH terms
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Animals
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Chemistry, Pharmaceutical / methods
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Drug Design
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Guanidines / chemistry*
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Humans
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Inhibitory Concentration 50
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Interleukin-1beta / antagonists & inhibitors
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Models, Chemical
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Molecular Structure
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Piperazine
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Piperazines / chemistry*
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Purinergic P2 Receptor Antagonists*
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Rats
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Receptors, Purinergic P2 / chemistry
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Receptors, Purinergic P2X7
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Structure-Activity Relationship
Substances
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Guanidines
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Interleukin-1beta
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P2RX7 protein, human
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P2rx7 protein, rat
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Piperazines
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Purinergic P2 Receptor Antagonists
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Receptors, Purinergic P2
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Receptors, Purinergic P2X7
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Piperazine
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dicyandiamido