1622148-63-3Relevant academic research and scientific papers
Orally Bioavailable Metal Chelators and Radical Scavengers: Multifunctional Antioxidants for the Coadjutant Treatment of Neurodegenerative Diseases
Kawada, Hiroyoshi,Kador, Peter F.
, p. 8796 - 8805 (2015/12/09)
Neurodegenerative diseases are associated with oxidative stress that is induced by the presence of reactive oxygen species and the abnormal cellular accumulation of transition metals. Here, a new series of orally bioavailable multifunctional antioxidants (MFAO-2s) possessing a 2-diacetylamino-5-hydroxypyrimidine moiety is described. These MFAO-2s demonstrate both free radical and metal attenuating properties that are similar to the original published MFAO-1s that are based on 1-N,N′-dimethylsulfamoyl-1-4-(2-pyrimidyl)piperazine. Oral bioavailability studies in C57BL/6 mice demonstrate that the MFAO-2s accumulate in the brain at significantly higher levels than the MFAO-1s while achieving similar neural retina levels. The MFAO-2s protect human neuroblastoma and retinal pigmented epithelial cells against hydroxyl radicals in a dose-dependent manner by maintaining cell viability and intracellular glutathione levels. The MFAO-2s outperform clioquinol, a metal attenuator that has been investigated for the treatment of Alzheimer's disease.
NEUROPROTECTIVE MULTIFUNCTIONAL ANTIOXIDANTS AND THEIR MONOFUNCTIONAL ANALOGS
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Paragraph 0066, (2014/09/03)
The neuroprotective multifunctional antioxidants are compounds that contain a 2-diacetylamino-5-hydroxypyrimidine moiety, having the structural formula: wherein R1 is CH2 or C2H4; R2 is H or —OR4 where R4 is H or aryl; and R3a and R3b are independently selected from the group consisting of H and —O-alkyl. The antioxidants are orally bioavailable metal-attenuating multifunctional antioxidants that can independently attenuate transition metals, as well as scavenger free radicals. The multifunctional antioxidant compounds, by their ability to independently chelate metals, such as Fe, Cu or Zn, and scavenge free radicals generated from different sources, are neuroprotective and are beneficial for the treatment of various neurological disorders, such as Alzheimer's disease, Parkinson's disease, ALS, traumatic brain injury, ocular disorders, such as cataract, glaucoma, age-related macular degeneration and other retinal degeneration, as well as for reducing the progression of diabetic complications.
