Methods and compositions for treating amyloid-related diseases
View Patent ↗Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
1. A compound of Formula V:
wherein:
A is nitrogen or oxygen;
R 11 is hydrogen, salt-forming cation, ester forming group, or when A is nitrogen, A and R 11 taken together form the residue of a natural or unnatural amino acid or a salt or ester thereof, wherein A and R 11 taken together are not a leucine residue;
n is 3 or 4;
aa is an amino acid residue selected from a natural amino acid residue selected from the group consisting of phenylalanine, tyrosine, or an unnatural amino acid residue selected from the group consisting of para-aminophenylalanine, para-bromophenylalanine, ortho-chlorophenylalanine, meta-chlorophenylalanine, para-chlorophenylalanine, meta-chlorotyrosine, 3,4-dichlorophenylalanine, 3,4-difluorophenylalanine, 3,5-diiodotyrosine, ortho-fluorophenylalanine, meta-fluorophenylalanine, para-fluorophenylalanine, meta-fluorotyrosine, homophenylalanine, homotyrosine, para-iodophenylalanine, 3-iodotyrosine, meta-methyltyrosine, para-nitrophenylalanine, 3-nitrotyrosine, ortho-phosphotyrosine, pentafluorophenylalanine, and phenylglycine wherein said amino acid residue is in the L configuration;
m is 1, 2, or 3;
R 14 is hydrogen or protecting group;
R 15 is hydrogen, alkyl or aryl; and pharmaceutically acceptable salts, esters, or prodrugs thereof.
2. The compound of claim 1 , wherein n is 4.
3. The compound of claim 1 , wherein n is 3.
4. The compound of claim 1 , wherein m is 1 or 2.
5. The compound of claim 4 , wherein m is 1.
6. The compound of claim 4 , wherein m is 2.
7. The compound of claim 1 , wherein A-R 11 is a residue of a natural amino acid, or a salt or ester thereof.
8. The compound of claim 7 , wherein A-R 11 is a phenylalanine residue.
9. The compound of claim 1 , wherein A is an oxygen and R 11 is a hydrogen or a salt-forming cation.
10. The compound of claim 1 , wherein aa is a residue of a natural amino acid.
11. The compound of claim 1 , wherein (aa) m is a residue of phenylalanine or phe-phe.
12. The compound of claim 1 , wherein aa is a residue of an unnatural amino acid.
13. The compound of claim 1 , wherein R 15 is hydrogen or substituted alkyl.
14. The compound of claim 13 , wherein R 15 is arylalkyl.
15. The compound of claim 13 , wherein R 15 is hydrogen.
16. The compound of claim 1 , wherein R 14 and R 15 are both hydrogen.
17. The compound of claim 1 , wherein said compound is selected from the group consisting of:
and pharmaceutically acceptable salts, esters, or prodrugs thereof.