Compounds for the treatment of diseases associated with amyloid or amyloid-like proteins
The present invention relates to novel compounds of formula (II) that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating, or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.
1. A compound having the general formula (IIa)
wherein
p is 2 or 3;
each linker K is independently C 1-3 alkylene which is optionally substituted by one or more C 1-4 alkyl groups;
the heterocyclic ring B is optionally substituted by one or more substituents selected from C 1-4 alkyl, C 1-4 alkoxy, mono- and di-C 1-4 alkyl amino, C 3-7 cycloalkyl amino, and 5- or 6-membered saturated heterocyclyl, or two substituents may be joined to form a saturated, unsaturated or aromatic 5- to 7-membered ring which is fused with the heterocyclic ring B;
R 1 is selected from —H, -halogen, —C 1-4 alkyl, —NH 2 , —NH—C 1-4 alkyl, —C 1-4 alkylene-NH 2 , —C 1-4 alkylene-NH—C 1-4 alkyl, -aryl, -aryl-R 3 , —C 1-4 alkylene-aryl, —C 1-4 alkylene-aryl-R 3 , -heteroaryl, -heteroaryl-R 3 , —NH—C 1-4 alkylene-aryl, —NH—C 1-4 alkylene-aryl-R 3 , —OH and —O—C 1-4 alkyl; and
R 3 is C 1-4 alkyl, halogen, OH or O—C 1-4 alkyl;
R 2 is —H, —C 1-4 alkyl, -aryl or a group of the formula (IIIa)
wherein B, K and R 1 are as defined above, q is 0 or 1 and r is 0 or 1.
2. The compound according to claim 1 , wherein each linker K is independently —CH 2 —, —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —.
3. The compound according to claim 1 , wherein R 1 is —H, —CH 3 , —NH—C 1-4 alkyl or —CH 2 —NH—CH 3 .
4. The compound according to claim 1 , wherein R 2 is a group of the formula (IIa).
5. A composition comprising a compound as defined in claim 1 .
6. A composition comprising the compound as defined in claim 1 and at least one further biologically active compound optionally in combination with a pharmaceutically acceptable carrier, a diluent, or an excipient.
7. A test kit for detection and/or diagnosis of an amyloid-associated disease or condition comprising the compound according to claim 1 .