Compounds and methods for the treatment of Alzheimer's disease and/or cerebral amyloid angiopathy
Described herein are novel compounds and methods for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA).
1. A compound having a structure represented by formula I:
wherein:
R 1 is H;
R 2 , R 4 are independently chosen from H, C 1 -C 8 alkyl, aryl, (CH 2 ) n aryl, (CH 2 ) n heteroaryl;
n=0-8;
X 1 is chosen from CO, SO, SO 2 , —CONH—, SO 2 NH—, SONH—;
A 1 is OR 4 .and
A 2 , B 1 , B 2 , C 1 , C 2 are independently chosen from H, OR 4 , F, wherein at least one of A 2 , B 1 , B 2 , C 1 or C 2 is F,
or a pharmaceutically acceptable salt or solvate thereof.
2. The compound of claim 1 , wherein R 4 is H.
3. The compound of claim 1 , wherein R 4 is benzyl.
4. The compound of claim 1 , wherein A 1 is OH.
5. The compound of claim 4 , wherein A 2 is H.
6. The compound of claim 1 , wherein B 1 is OR 4 .
7. The compound of claim 6 , wherein B 1 is OH.
8. The compound of claim 7 , wherein B 2 is H.
9. The compound of claim 1 , wherein A 1 is OH, A 2 is H, B 1 is OH and B 2 is H.
10. A pharmaceutical composition comprising:
a. the compound of claim 1 ; and
b. at least one pharmaceutically acceptable carrier.
11. A method for treating Alzheimer's disease and/or cerebral amyloid angiopathy in a patient at risk for developing or diagnosed with the same, the method comprising administering to the patient an effective amount of the compound of claim 1 .
12. The method of claim 11 , wherein the administration of an effective amount of the compound increases processing of one or more gangliosides selected from GM2 and GA2.
13. The method of claim 11 , wherein the patient is at risk of developing or diagnosed with Alzheimer's disease.
14. The method of claim 11 , wherein the patient is at risk of developing or diagnosed with cerebral amyloid angiopathy.
15. A method for enhancing the activity of β-hexosaminidase, the method comprising administering an effective amount of the compound of claim 1 .
16. A kit comprising:
a. the compound of claim 1 ; and
b. instructing for using the same to treat Alzheimer's disease and/or cerebral amyloid angiopathy.