402519-04-4Relevant articles and documents
An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury
Velentza, Anastasia V.,Wainwright, Mark S.,Zasadzki, Magdalena,Mirzoeva, Salida,Schumacher, Andrew M.,Haiech, Jacques,Focia, Pamela J.,Egli, Martin,Watterson, D. Martin
, p. 3465 - 3470 (2003)
Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury attenuated brain tissue or neuronal biomarker loss measured, respectively, 1 week and 3 days later. Because aminopyridazine is a privileged structure in neuropharmacology, we determined the high-resolution crystal structure of a binary complex between the kinase domain and a molecular fragment of the DAPK inhibitor. The co-crystal structure describes a structural basis for interaction and provides a firm foundation for structure-assisted design of lead compounds with appropriate molecular properties for future drug development.
Myosin light chain kinase inhibitor compounds, compostions and related methods of use
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Page/Page column title page; 12-13; 1/3, (2008/06/13)
Pyridazinyl compounds, compositions and related methods of use.
Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic antineuroinflammatory compound
Mirzoeva, Salida,Sawkar, Anu,Zasadzki, Magdalena,Guo, Ling,Velentza, Anastasia V.,Dunlap, Vincent,Bourguignonl, Jean-Jacques,Ramstrom, Helena,Haiech, Jacques,Van Eldik, Linda J.,Watterson
, p. 563 - 566 (2007/10/03)
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-1β, iNOS, and NO production by activated glia, without inhibition of potentially beneficial glial functions.
