Abstract
Excessive glial activation, with overproduction of cytokines and oxidative stress products, is detrimental and a hallmark of neurodegenerative disease pathology. Suppression of glial activation is a potential therapeutic approach, and protein kinases are targets of some antiinflammatory drugs. To address an unmet need for selective inhibitors of glial activation, we developed a novel 3-amino-6-phenylpyridazine derivative that selectively blocks increased IL-1 beta, iNOS, and NO production by activated glia, without inhibition of potentially beneficial glial functions.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Astrocytes / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Cells, Cultured
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Central Nervous System Agents / chemical synthesis*
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Central Nervous System Agents / chemistry
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Central Nervous System Agents / pharmacology
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Interleukin-1 / antagonists & inhibitors
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Microglia / drug effects
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / metabolism
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase Type II
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Central Nervous System Agents
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Enzyme Inhibitors
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Interleukin-1
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Pyridazines
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Nitric Oxide
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, rat
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases