Piperidine derivatives as HDAC1/2 inhibitors
Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity.
1. A compound having the structure of Formula IIIa:
or a pharmaceutically acceptable salt thereof
wherein,
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 and R 5 together form a heterocyclyl selected from the group consisting of morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl, wherein the morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl are optionally substituted by 1 or 2 of C 1 -C 6 -alkyl,halo, or hydroxy.
2. The compound of claim 1 , wherein R 1 is H.
3. The compound of claim 1 , wherein R 2 is H.
4. The compound of claim 1 , wherein R 3 is H, methyl, ethyl, isopropyl, or phenyl.
5. The compound of claim 1 selected from:
ID
Structure
004
005
006
013
015
016
017
019
020
021
022
023
024
025
028
030
031
032
and pharmaceutically acceptable salts thereof.
6. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
7. A method for treating a disease mediated by HDAC1 and/or HDAC2 in a subject comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the disease mediated by HDAC1 and/or HDAC2 in is selected from a group consisting of sickle-cell disease, beta-thalassemia, lung cancer, colon cancer, breast cancer, breast cancer, neuroblastoma, leukemia or lymphoma.