Substituted fluorine-containing imidazole salt compound, preparation method therefor, pharmaceutical composition thereof and use thereof
Disclosed in the invention are a type of compounds having activity of activating 5′-adenosine monophosphate-activated protein kinase (AMPK), a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for reducing fatty acid synthesis, for inhibiting triglyceride and cholesterol synthesis, for preventing and/or treating obesity and type II diabetes, for preventing and/or treating tumor, for preventing and/or treating Parkinson's disease, for preventing and/or treating Alzheimer's disease or for prolonging the lifespan of mammals:
1 . A compound of a formula
wherein,
R 1 is a C16-C18 alkyl substituted by 11, 13 or 15 fluorine atoms;
R 2 is selected from H, C1-C6 alkyl, and C3-C6 cycloalkyl;
S 1 is selected from 1′-halogen and 1′-C1-C6 alkoxy;
S 2 is selected from: 4′-halogen and 5′-halogen; and
X − is an anion of a pharmaceutically acceptable inorganic or organic acid salt;
or a pharmaceutically acceptable salt thereof.
2 . The compound according to claim 1 , which is selected from:
No.
Structure
IB-30
IB-31
IB-32
IB-33
IB-34
IB-35
IB-36
IB-37
IB-38
IB-39
IB-40
IB-41
IB-42
IB-43
IB-44
IB-45
IB-46
IB-47
IB-48
IB-49
IB-50
IB-51
IB-52
IB-53
IB-54
IB-55
IB-56
IB-57
IB-58
IB-59
and IB-60
or a prodrug thereof, a pharmaceutically acceptable salt thereof.
3 . A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
4 . A pharmaceutical composition comprising the compound according to claim 2 , or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable excipient.
5 . The compound according to claim 1 ,
wherein R 2 is H, a C1-C3 alkyl, or a C3-C4 cycloalkyl; or
wherein X − is selected from a group consisting of chloride ion, bromide ion, iodide ion, bisulfate ion, sulfate ion, phosphate ion, maleate ion, fumarate ion, tartrate ion, palmitate ion, oxalate ion, citrate ion, succinate ion, methanesulfonate ion, benzenesulfonate ion, and p-toluenesulfonate ion.
6 . The compound according to claim 1 ,
wherein R 1 is selected from the group consisting of C 16 F 11 H 22 —, and C 17 F 13 H 22 —; or
wherein R 2 is selected from the group consisting of H, methyl, isopropyl, and cyclopropyl; or
wherein S 1 is a 1′-C1-C3 alkoxy.
7 . The compound according to claim 1 , wherein R 1 is selected from the group consisting of n-C 16 F 11 H 22 —, and n-C 17 F 13 H 22 —.
8 . The composition according to claim 3 , wherein the composition further comprises a pharmaceutically acceptable excipient.
9 . The composition according to claim 1 , wherein S 1 is selected from 1′-halogen, and 1′-C1-C3 alkoxy.