Benfotiamine derivatives, method for preparing the same and pharmaceutical composition comprising the same
The present disclosure relates to benfotiamine derivatives, a method for preparing the same and a pharmaceutical composition, as indicated below, comprising the same. In the present disclosure, when the ortho position of benzene ring is only a halogen atom or an ethoxy substitution, or the meta position is only a bromine 5 atom, a chlorine atom, a fluorine atom or a nitro substitution, or the para position is only a chlorine atom, a methoxy substitution or a nitro substitution, its compound has a significant inhibition effect on Aβ40 and Aβ42. Furthermore, when the ortho position of benzene ring is only a fluorine atom or a bromine atom substitution, the compound has an outstanding inhibition effect on Aβ40 and Aβ42.
1. A benfotiamine derivative represented by formula (1)
wherein
each one of R 2 , R 3 , R 4 and R 5 is hydrogen atom, and R 1 is fluorine atom, bromine atom or alkoxy group; or
each one of R 1 , R 3 , R 4 and R 5 is hydrogen atom, and R 2 is fluorine atom, bromine atom or nitro group.
2. The benfotiamine derivative according to claim 1 , wherein each one of R 2 , R 3 , R 4 and R 5 is hydrogen atom, and R 1 is ethoxy group.
3. The benfotiamine derivative according to claim 1 , wherein each one of R 1 , R 3 , R 4 and R 5 is hydrogen atom, and R 2 is bromine atom.
4. A method for producing the benfotiamine derivative according to claim 1 , comprising reacting a compound of monophosphothiamine shown in formula (Ia) with a compound of benzoyl chloride shown in formula (Ib),
wherein,
each one of R 2 , R 3 , R 4 and R 5 is hydrogen atom, and R 1 is fluorine atom, bromine atom or alkoxy group; or
each one of R 1 , R 3 , R 4 and R 5 is hydrogen atom, and R 2 is fluorine atom, bromine atom or nitro group.
5. A method of treating Alzheimer's disease, comprising administering the benfotiamine derivative according to claim 1 to a subject in need thereof.