Martinez-Viturro, Carlos M. published the artcileDiazaspirononane Nonsaccharide Inhibitors of O-GlcNAcase (OGA) for the Treatment of Neurodegenerative Disorders, Recommanded Product: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, the main research area is azaspirononane OGA inhibitor neurodegenerative disorder Alzheimer bacterial hydrolase ortholog.
O-GlcNAcylation is a post-translational modification of tau understood to lower the speed and yield of its aggregation, a pathol. hallmark of Alzheimer’s disease (AD). O-GlcNAcase (OGA) is the only enzyme that removes O-linked N-acetyl-D-glucosamine (O-GlcNAc) from target proteins. Therefore, inhibition of OGA represents a potential approach for the treatment of AD by preserving the O-GlcNAcylated tau protein. Herein, we report the multifactorial optimization of high-throughput screening hit 8 to a potent, metabolically stable, and orally bioavailable diazaspirononane OGA inhibitor (+)-56. The human OGA X-ray crystal structure has been recently solved, but bacterial hydrolases are still widely used as structural homologues. For the first time, we reveal how a nonsaccharide series of inhibitors binds bacterial OGA and discuss the suitability of two different bacterial orthologues as surrogates for human OGA. These breakthroughs enabled structure-activity relationships to be understood and provided context and boundaries for the optimization of druglike properties.
Journal of Medicinal Chemistry published new progress about Alzheimer disease. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Recommanded Product: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine.
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics