title: 6-acetyl-5H-thiazolo[3,2-a]pyrimidine derivatives as the novel acetylcholinesterase inhibitors: design, synthesis, and biological activity.
abstract: Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer's drugs. A series of 6-acetyl- 5H-thiazolo[3,2-a]pyrimidine derivatives as the novel acetylcholinesterase inhibitors were designed based on virtual screening methods. The target compounds which are not reported in the literature were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, 1H-NMR and 13C-NMR. The biological evaluation against human acetylcholinesterase in vitro showed most of the target compounds exhibited varying inhibition at 10 µM using the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer's disease, and a foundation in search for improved acetylcholinesterase inhibitors with the novel scaffolds. The preliminary structure-activity relationships were the 2-hydroxyethoxy group at the phenyl ring at C4 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds.
authors.affiliation: Department of Chinese Medicine Chemistry, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhi
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Cheng
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Erfang
authors.initials: E
authors.lastname: Huang
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.forename: Huangquan
authors.initials: H
authors.lastname: Lin
authors.forename: David Chicheong
authors.initials: DC
authors.lastname: Wan
authors.forename: Chun
authors.initials: C
authors.lastname: Hu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000110:Acetylcholinesterase