P62-ZZ small molecule modulators

1. A compound, or a pharmaceutically acceptable salt thereof, having a formula I of:

wherein Ar is benzenetriyl;

R 1 has a structure of: CH 2 —X—(CH 2 ) m —R 11 , wherein X is NH or O, m is 0 to 6, and R 11 is optionally-substituted cycloalkyl;

each R 2 is the same or different and has a structure of:

wherein Z is —O—;

Z 1 is (—CH 2 —) m ;

Cy is phenyl; and

each R 4 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, or amino; and c is 1 to 5; and

each R 3 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, amino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or a nitro,

wherein a is 2, and b is 0.

2. The compound of claim 1 , wherein a first R 2 group is in a meta position on the Ar ring relative to the R 1 group, and a second R 2 group is in a para position on the Ar ring relative to the R 1 group.

3. The compound of claim 1 , wherein R 4 is —F, —Cl, —OCH 3 , —OH, —CH 3 or —NH 2 .

4. The compound of claim 1 , wherein c is 1 and R 4 is 4-fluoro, or 4-methyl.

5. The compound of claim 1 , wherein c is 2 and R 4 is 2, 4-difluoro.

6. The compound of claim 1 , wherein R 11 is

and m is 0 or 1.

7. The compound of claim 1 , wherein each R 2 group has the same structure.

8. The compound of claim 1 , having a structure of:

wherein each of R 7 , R 8 , and R 9 are the same or different and are selected from —F, —Cl, —OCH 3 , —OH, —CH 3 , or —NH 2 ; d is 0; e is 1 to 5; f is 1 to 5; m is 0 or 1; and R 11 is optionally-substituted cycloalkyl.

9. The compound of claim 1 , having a structure of:

wherein each of R 7 , R 8 , and R 9 are the same or different and are selected from —F, —Cl, —OCH 3 , —OH, —CH 3 , or —NH 2 ; d is 0 to 3; e is 1 to 5; f is 1 to 5; m is 0 or 1; and R 11 is optionally-substituted cycloalkyl.

10. The compound of claim 8 , wherein R 11 is

11. The compound of claim 1 , selected from:

12. A compound, or a pharmaceutically acceptable salt thereof, having a formula I of:

wherein Ar is benzenetriyl;

R 1 has a structure of:

wherein W is —CH 2 —;

X is —NR 5 —, wherein R 5 is H or an alkyl, or —O—; and

Y is

each R 2 is the same or different and has a structure of:

wherein Z is —O—;

Z 1 is (—CH 2 —) m wherein m is 1; Cy is phenyl; and

each R 4 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, or amino; and c is 0 to 5; and

each R 3 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, amino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or a nitro,

wherein a is 2 to 5, and b is 0 to 3.

13. The compound of claim 12 , wherein X is —NR 5 —, wherein

R 5 is H.

14. The compound of claim 1 , wherein the compound is:

15. The compound of claim 12 , wherein a is 2 and b is 0.

16. The compound of claim 12 , wherein R 4 is —F, —Cl, —OCH 3 , —OH, —CH 3 or —NH 2 .

17. The compound of claim 12 , wherein c is 1 and R 4 is 4-fluoro, or 4-methyl.

18. The compound of claim 12 , wherein c is 2 and R 4 is 2, 4-difluoro.