US 11,702,389 B2
Piperidine derivatives as HDAC1/2 inhibitors
John H. van Duzer, Concord, MA (US); and Ralph Mazitschek, Weston, MA (US)
Assigned to REGENACY PHARMACEUTICALS, LLC, Waltham, MA (US)
Filed by Regenacy Pharmaceuticals, LLC, Waltham, MA (US)
Filed on Feb. 24, 2021, as Appl. No. 17/184,118.
Application 17/184,118 is a division of application No. 16/433,386, filed on Jun. 6, 2019, granted, now 10,968,180.
Application 15/700,998 is a division of application No. 14/966,556, filed on Dec. 11, 2015, granted, now 9,790,180, issued on Oct. 17, 2017.
Application 16/433,386 is a continuation of application No. 15/700,998, filed on Sep. 11, 2017, granted, now 10,358,421, issued on Jul. 23, 2019.
Claims priority of provisional application 62/238,931, filed on Oct. 8, 2015.
Claims priority of provisional application 62/091,221, filed on Dec. 12, 2014.
Prior Publication US 2021/0179559 A1, Jun. 17, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 211/58 (2006.01); C07D 409/12 (2006.01); C07D 409/14 (2006.01); C07D 401/14 (2006.01); C07D 401/12 (2006.01)
CPC C07D 211/58 (2013.01) [C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 409/12 (2013.01); C07D 409/14 (2013.01)] 19 Claims
 
1. A method for treating a disease mediated by HDAC1 and/or HDAC2 in a subject comprising administering to the subject a compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein,
X1 is CR7 or N;
X2 is CH or N;
wherein X1 and X2 are each N, or X1 and X2 are each CH;
Y is selected from the group consisting of:

OG Complex Work Unit Chemistry
Z is selected from the group consisting of H, C1-C6-alkyl, C6-aryl, C(O)NR4R5, C(O)OR6, C(O)C1-C6-alkyl, C(O)C0-C6-alkyl-C6-aryl, C(O)—C3-C6-cycloalkyl, C(O)—C2-C6-heterocyclyl, and C(O)C0-6-alkyl-heteroaryl, wherein the aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted by 1 or 2 of C1-C6-alkyl, halo, C1-C6-haloalkyl, hydroxy, or C1-C6-alkoxy;
Ra and Rb are H, or Ra and Rb together form a fused C6-aryl;
R1 is selected from the group consisting of H and C1-C6-alkyl;
R2 is selected from the group consisting of H, C1-C6-alkyl, and C6-aryl;
R3 is selected from the group consisting of H, C1-C6-alkyl, and C6-aryl;
or R2 and R3 together form a C2-C6-heterocyclyl;
R4 is selected from the group consisting of H, C1-C6-alkyl, C1-C6-alkyl-OH, and C1-C6—NH2;
R5 is C1-C6-alkyl;
or R4 and R5 together form a C2-C6-heterocyclyl, wherein heterocyclyl is optionally substituted by 1 or 2 of C1-C6-alkyl, halo, C1-C6-haloalkyl, hydroxy, or C1-C6-alkoxy;
R6 is selected from the group consisting of C1-C6-alkyl and C0-C6-alkyl-C6-aryl, wherein aryl is optionally substituted by 1 or 2 of C1-C6-alkyl, halo, or hydroxy; and
R7 is H;
wherein the disease mediated by HDAC1 and/or HDAC2 is selected from the group consisting of sickle-cell disease, beta-thalassemia, lung cancer, colon cancer, neuroblastoma, leukemia, and lymphoma.