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 (VII):
or a pharmaceutically acceptable salt thereof; wherein
A 6 is optionally substituted aryl;
each R d is independently selected from the group consisting of hydrogen and optionally substituted C 1 -C 10 alkyl;
R 16 and R 17 are each independently selected from the group consisting of hydrogen and optionally substituted C 1 -C 10 alkyl;
Z 6 is NR c R c ; and
each R c is independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 10 alkyl, optionally substituted C 2 -C 10 alkenyl, optionally substituted C 2 -C 10 alkynyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 3 -C 12 cycloalkenyl, optionally substituted heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl; alternatively, two R c groups are taken together with the atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic.
2. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein A 6 is optionally substituted phenyl, or a pharmaceutically acceptable salt thereof.
5. The compound of claim 4 , wherein Z 6 is NR c R c and wherein the two R c groups are taken together with the atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic, or a pharmaceutically acceptable salt thereof.