title: Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic antineuroinflammatory compound.
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.
authors.forename: Salida
authors.initials: S
authors.lastname: Mirzoeva
authors.forename: Anu
authors.initials: A
authors.lastname: Sawkar
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zasadzki
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Velentza
authors.forename: Vincent
authors.initials: V
authors.lastname: Dunlap
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Bourguignon
authors.forename: Helena
authors.initials: H
authors.lastname: Ramstrom
authors.forename: Jacques
authors.initials: J
authors.lastname: Haiech
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
authors.forename: D Martin
authors.initials: DM
authors.lastname: Watterson
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D017628:Microglia / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002491:Central Nervous System Agents; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D011724:Pyridazines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases