Proteostasis regulators
The present invention is directed to compounds having the Formulae (Ia-Ie), (II), (IIIa-IIId), (IVa-IVc), (Va-Vb), (VIa-VIe), (VII), (VIIIa-VIIIc), and (IX), pharmaceutically acceptable salts, prodrugs and solvates thereof, compositions of any of thereof and methods for the treatment of a condition associated with a dysfunction in proteostasis comprising an effective amount of these compounds.
1. A compound having the Formula (II):
or a pharmaceutically acceptable salt, or solvate thereof, wherein:
D is optionally substituted phenyl;
Q is C(R d );
each R i is independently selected from the group consisting of hydrogen and optionally substituted C 1 -C 10 alkyl;
R 5 and R 6 are each independently selected from the group consisting of hydrogen and optionally substituted C 1 -C 10 alkyl;
Z 1 is NR c R c ;
each R c is independently selected from the group consisting of hydrogen and optionally substituted C 1 -C 10 alkyl; or alternatively, the two R c groups are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic; and
R d is optionally substituted C 1 -C 10 alkyl.
2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof.
3. A compound selected from those shown in the Table below, or a pharmaceutically acceptable salt or solvate thereof:
Compound
A34
A36
A38
4. The compound of claim 1 , wherein the two R c groups are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic, or a pharmaceutically acceptable salt or solvate thereof.
5. The compound of claim 1 , wherein R d is methyl, or a pharmaceutically acceptable salt or solvate thereof.