p62-ZZ chemical inhibitor
A method for treating a p62-mediated disease (e.g., multiple myeloma) in a subject, the method comprising administering to the subject a therapeutically effective amount of at least one p62-ZZ inhibitor compound.
1. A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of Formula I:
wherein Ar is an arylene;
R 1 has a structure of:
wherein W is an alkanediyl,
X is —NR 5 —, R 5 is H, and
Y is a hydroxyalkyl;
each R 2 is the same or different and has a structure of:
wherein Z is —NR 6 , R 6 is H,
Z 1 is (—CH 2 —),
Cy is a 6-membered aryl ring, and
each R 4 is the same halogen, and wherein c is 1, and a is 2.
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. A compound, or a pharmaceutically acceptable salt or ester thereof, having a structural Formula II:
wherein each of R 7 , R 8 , and R 9 is the same or different and is selected from —F, —Cl, —OCH 3 , —OH, —CN, or —NH 2 ;
d is 0 to 3;
e is 0 to 5; and
f is 0 to 5,
provided that the compound is not:
4. The compound of claim 3 , wherein d is 0.
5. The compound of claim 4 , wherein e and f are each independently 1.
6. The compound of claim 5 , wherein R 8 is —F.
7. The compound of claim 6 , wherein R 9 is —F.
8. The compound of claim 7 , wherein R 8 and R 9 are each independently situated in the para position on the phenyl ring.
9. The compound of claim 3 , wherein the compound is
10. A composition comprising a compound of Formula (I) of claim 1 and pharmaceutically acceptable carrier.
11. A composition comprising a compound of Formula (II) of claim 3 and pharmaceutically acceptable carrier.