Hoang, Van-Hai published the artcileDiscovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design, Related Products of pyrimidines, the publication is Journal of Medicinal Chemistry (2017), 60(6), 2573-2590, database is CAplus and MEDLINE.
Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer’s disease (AD). The authors designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ3E-42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 (I) significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an addnl. binding region into the authors’ previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu 327 in the QC binding site. The authors’ study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.
Journal of Medicinal Chemistry published new progress about 174456-28-1. 174456-28-1 belongs to pyrimidines, auxiliary class Pyrimidine,Alkynyl,Alcohol, name is 3-(Pyrimidin-5-yl)prop-2-yn-1-ol, and the molecular formula is C7H6N2O, Related Products of pyrimidines.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia