Compounds and compositions for the detection and treatment of Alzheimer's disease and related disorders
View Patent ↗One aspect of the present invention relates to compounds, compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyloidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.
1. A compound, or a pharmaceutically acceptable salt thereof, represented by formula I:
wherein, independently for each occurrence,
X is —O—;
Y is —C(R 1 ) 2 —;
L is —R 3 , —C(═O)R 3 , —C(═O)[C(R 1 ) 2 ] p R 3 , or —[C(R 1 ) 2 ] p C(═O)R 3 ;
R 1 is hydrogen, halo, alkyl, haloalkyl, perhaloalkyl, fluoroalkyl, perfluoroalkyl, hydroxy, or alkoxy;
R 2 is an unsubstituted alkyl, or alkyl substituted with one or more substituents selected from the group consisting of halo, hydroxy, alkoxy, and amino;
R 3 is
R 4 is hydrogen, halo, alkyl, haloalkyl, perhaloalkyl, fluoroalkyl, perfluoroalkyl, hydroxy, or alkoxy;
m is 1, 2 or 3;
n is 1, 2 or 3;
m plus n is 3 or 4; and
p is 1-10 inclusive.
2. The compound of claim 1 , wherein R 1 or R 4 is halo, or R 1 , R 2 , or R 4 comprises at least one halo substituent; and the halo or the halo substituent is selected from the group consisting of 18 F, 76 Br, 77 Br, 123 I, 124 I and 125 I.
3. The compound of claim 1 , wherein R 2 is unsubstituted alkyl, or alkyl substituted with —F, —Cl, —Br or —I.
4. The compound of claim 1 , wherein R 3 is
5. The compound of claim 1 , wherein R 3 is
6. The compound of claim 1 , wherein R 3 is
7. The compound of claim 1 , wherein L is —C(═O)R 3 ; and one instance of R 4 is — 18 F.
8. The compound of claim 1 , wherein L is —C(═O)R 3 ; R 3 is
and R 2 is unsubstituted alkyl.
9. The compound of claim 1 , wherein L is —C(═O)R 3 ; R 3 is
and R 2 is ethyl.
10. The compound of claim 1 , wherein the compound is represented by
11. A compound, or a pharmaceutically acceptable salt thereof, represented by formula I:
wherein, independently for each occurrence,
X is —O—;
Y is —C(R 1 ) 2 —;
L is —R 3 ;
R 1 is hydrogen, halo, alkyl, haloalkyl, perhaloalkyl, fluoroalkyl, perfluoroalkyl, hydroxy, or alkoxy;
R 2 is alkyl substituted with one or more —F;
R 3 is alkyl or heteroalkyl;
m is 1, 2 or 3;
n is 1, 2 or 3;
m plus n is 3 or 4; and
p is 1-10 inclusive.
12. The compound of claim 11 , wherein
(a) R 1 is halo, or R 1 or R 3 comprises at least one halo substituent; and the halo or the halo substituent is selected from the group consisting of 18 F, 76 Br, 77 Br, 123 I, 124 I and 125 I; or
(b) R 2 is alkyl substituted with — 18 F.
13. The compound of claim 11 , wherein R 2 is alkyl substituted with — 18 F.
14. The compound of claim 11 , wherein R 2 is alkyl substituted with — 18 F; and R 3 is alkyl.
15. The compound of claim 11 , wherein the compound is represented by