PIPERIDINE DERIVATIVES AS HDAC1/2 INHIBITORS

1 . A compound of Formula I:

or a pharmaceutically acceptable salt thereof,

wherein,

X 1 is CR 7 or N;

X 2 is CH or N;

Y is selected from the group consisting of:

Z is selected from the group consisting of H, C 1 -C 6 -alkyl, C 6 -aryl, C(O)NR 4 R 5 , C(O)OR 6 , C(O)C 1 -C 6 -alkyl, C(O)C 0 -C 6 -alkyl-C 6 -aryl, C(O)—C 3 -C 6 -cycloalkyl, C(O)—C 2 -C 6 -heterocyclyl, and C(O)C 0 -C 6 -alkyl-heteroaryl, wherein the aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted by 1 or 2 of C 1 -C 6 -alkyl, halo, C 1 -C 6 -haloalkyl, hydroxy, or C 1 -C 6 -alkoxy;

R a and R b are H, or R a and R b together form a fused C 6 -aryl;

R 1 is selected from the group consisting of H and C 1 -C 6 -alkyl;

R 2 is selected from the group consisting of H, C 1 -C 6 -alkyl, and C 6 -aryl;

R 3 is selected from the group consisting of H, C 1 -C 6 -alkyl, and C 6 -aryl;

or R 2 and R 3 together form a C 2 -C 6 -heterocyclyl;

R 4 is selected from the group consisting of H, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-OH, and C 1 -C 6 —NH 2 ;

R 5 is C 1 -C 6 -alkyl;

or R 4 and R 5 together form a C 2 -C 6 -heterocyclyl, wherein heterocyclyl is optionally substituted by 1 or 2 of C 1 -C 6 -alkyl, halo, C 1 -C 6 -haloalkyl, hydroxy, or C 1 -C 6 -alkoxy;

R 6 is selected from the group consisting of C 1 -C 6 -alkyl and C 0 -C 6 -alkyl-C 6 -aryl, wherein aryl is optionally substituted by 1 or 2 of C 1 -C 6 -alkyl, halo, or hydroxy; and

R 7 is selected from the group consisting of H, C 1 -C 6 -alkyl, and C 3 -C 6 -cycloalkyl.

2 . The compound of claim 1 , having the structure of Formula II:

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 1 , wherein X 1 and X 2 are each N, or X 1 and X 2 are each CH.

4 . The compound of claim 1 , wherein Y is:

5 . The compound of claim 1 , wherein Z is selected from the group consisting of C(O)NR 4 R 5 , C(O)OR 6 , C(O)—C 3 -C 6 -cycloalkyl, C(O)—C 2 -C 6 -heterocyclyl, and C(O)C 0 -C 6 -alkyl-heteroaryl, wherein heteroaryl, cycloalkyl, or heterocyclyl are optionally substituted by 1 or 2 of C 1 -C 6 -alkyl, halo, or hydroxy; and

R 6 is C 6 -aryl.

6 . The compound of claim 1 , wherein Z is selected from the group consisting of H, C 1 -C 6 -alkyl, and C 6 -aryl.

7 . The compound of claim 1 , wherein R 1 is H.

8 . The compound of claim 1 , wherein R 2 is H.

9 . The compound of claim 1 , wherein R 3 is H, methyl, ethyl, isopropyl, or phenyl.

10 - 16 . (canceled)

17 . The compound of claim 1 selected from:

or pharmaceutically acceptable salts thereof.

18 . (canceled)

19 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

20 . A method for inhibiting the activity of HDAC1 and/or HDAC2 in a subject, comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

21 - 29 . (canceled)

30 . A method for treating a disease or disorder associated with GATA binding protein 2 (Gata2) deficiency comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically salt thereof.

31 . A method for increasing GATA binding protein 2 (Gata2) expression in a cell comprising contacting the cell with a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

32 . The method of claim 31 , wherein Gata2 overexpression induces HbG (gamma globin).

33 . A method for inducing HbG (gamma globin) expression in a subject, comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

34 . The method of claim 33 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered in a dosage resulting in about a 2-fold to about a 20-fold increase in HbG in the subject.