Semenov, Vyacheslav E.; Zueva, Irina V.; Mukhamedyarov, Marat A.; Lushchekina, Sofya V.; Kharlamova, Alexandra D.; Petukhova, Elena O.; Mikhailov, Anatoly S.; Podyachev, Sergey N.; Saifina, Lilya F.; Petrov, Konstantin A.; Minnekhanova, Oksana A.; Zobov, Vladimir V.; Nikolsky, Evgeny E.; Masson, Patrick; Reznik, Vladimir S. published an article in 2015, the title of the article was 6-Methyluracil Derivatives as Bifunctional Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease.Application of 626-48-2 And the article contains the following content:
Novel 6-methyluracil derivatives with ω-(substituted benzylethylamino)alkyl chains at the nitrogen atoms of the pyrimidine ring were designed and synthesized. The numbers of methylene groups in the alkyl chains were varied along with the electron-withdrawing substituents on the benzyl rings. The compounds are mixed-type reversible inhibitors of cholinesterases, and some of them show remarkable selectivity for human acetylcholinesterase (hAChE), with inhibitory potency in the nanomolar range, more than 10,000-fold higher than that for human butyrylcholinesterase (hBuChE). Mol. modeling studies indicate that these compounds are bifunctional AChE inhibitors, spanning the enzyme active site gorge and binding to its peripheral anionic site (PAS). In vivo experiments show that the 6-methyluracil derivatives are able to penetrate the blood-brain barrier (BBB), inhibiting brain-tissue AChE. The most potent AChE inhibitor, (1,3-bis[5-(o-nitrobenzylethylamino)pentyl]-6-methyluracil), was found to improve working memory in scopolamine and transgenic APP/PS1 murine models of Alzheimer’s disease, and to significantly decrease the number and area of β-amyloid peptide plaques in the brain. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Application of 626-48-2
The Article related to methyluracil derivative preparation acetylcholinesterase inhibitor alzheimer disease treatment, 6-methyluracil, alzheimer’s disease, acetylcholinesterase, molecular modeling, reversible inhibitors and other aspects.Application of 626-48-2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia