The invention relates to a
tricyclic thiazolopyrimidine
ketone ether derivative and application thereof.The derivative is prepared by the steps that
ethyl cyanoacetate serves as an initial
raw material, a
hydroxylamine compound (A) is generated under the action of
sodium nitrite and
phosphoric acid, 2-amino
ethyl cyanoacetate (B) is obtained through reduction, the 2-amino
ethyl cyanoacetate (B) reacts with
acetic anhydride and a Lawesson
reagent to obtain a 5-amino-4-
formate thiazole compound (D), and the 5-amino-4-
formate thiazole compound (D) reacts with the
sodium nitrite and the
phosphoric acid to obtain the
tricyclic thiazolopyrimidine
ketone ether derivative. The preparation method comprises the following steps: taking 4-bromo-5, 7, 8, 9-tetrahydrothiazole [5 ', 4': 4, 5]
pyrimidine [1, 2-a]
azepine-11 (5H)-
ketone as a
raw material, performing NBS bromination to obtain a 2-bromo-dihydropyrrole [1, 2-a] thiazolo [5, 4-d]
pyrimidine-9 (5H)-ketone compound (F) and a 2-bromo-6, 7, 8, 9-tetrahydrothiazole [5 ', 4': 4, 5]
pyrimidine [1, 2-a]
azepine-11 (5H)-ketone derivative (G) under the action of
phosphorus oxychloride, and finally reacting with different substituted
phenols (
thiophenol) under the action of alkali to obtain 40
tricyclic thiazole pyrimidine ketone
ether compounds H1-H20 and I1-I20. The invention also investigates the inhibitory activity of the 40 compounds on acetylcholin
esterase and butyrylcholin
esterase in Alzheimer's
disease, and the result shows that 20 compounds have strong inhibitory activity on acetylcholin
esterase, and 22 compounds have strong inhibitory activity on butyrylcholin esterase.