HDAC inhibitors and methods of treatment using the same

Patent metadata

Field	Value
Publication number	US-11149062-B2
Application number	US-201515755701-A
Country	US
Kind code	B2
Filing date	Oct 29, 2015
Priority date	Aug 28, 2015
Publication date	Oct 19, 2021
Grant date	Oct 19, 2021

Abstract

Disclosed herein are novel HDAC inhibitors. The HDAC inhibitors may be used in methods of treating cancer. The HDAC inhibitors may be used in methods of treating a neurological disorder.

First claim

The invention claimed is:

1. A compound according to Formula (I):

or a stereoisomer or salt thereof;
wherein X is NH or O or a direct bond;
R 1 is H, C 1-10 alkyl, aryl, heteroaryl, or —NH—CHR a C(O)—OR 4 ;
R a is an amino acid side chain, H, C 1-10 alkyl, C 1-10 heteroalkyl, aryl, or heteroaryl;
R 4 is H, C 1-10 alkyl, heteroaryl or aryl;
R 2 is SH, SeH, or C(O)NHOH, or the compound forms a disulfide or diselenide dimer at the R 2 position;
R 3 is H, C 1-10 alkyl, heteroaryl, aryl, or —C(O)R 5 ;
R 5 is C 1-10 alkyl, heteroaryl, aryl, or —CH(N(R N ) 2 )(CR′R″OR O );
R′ is H or C 1-10 alkyl, heteroaryl, or aryl;
R″ is H or C 1-10 alkyl, heteroaryl, or aryl;
each R N is independently H, C 1-10 alkyl, heteroaryl, or aryl;
R O is H, C 1-10 alkyl, heteroaryl, or aryl;
Y is H, C 1-10 alkyl, heteroaryl, aryl, or halogen;
n is an integer from 0 to 5;
wherein if X is a direct bond, then R 1 is —NH—CHR a C(O)—OR 4 ; and
wherein the dashed bond indicates the presence of an optional double bond.

2. The compound according to claim 1 selected from the group consisting of

or a stereoisomer or salt thereof.

3. The compound according to claim 1 , or a stereoisomer or salt thereof, wherein X is a direct bond and R 1 is —NH—CHR a C(O)—OR 4 .

4. The compound according to claim 3 , or a stereoisomer or salt thereof, wherein R 2 is SH or C(O)NHOH.

5. The compound according to claim 3 , or a stereoisomer or salt thereof, wherein Y is H and R 3 is H or —C(O)R 5 .

6. The compound according to claim 1 , or a stereoisomer or salt thereof, wherein X is O and R 1 is H, C 1-10 alkyl, aryl, or heteroaryl.

7. The compound according to claim 6 , or a stereoisomer or salt thereof, wherein R 2 is SH or C(O)NHOH.

8. The compound according to claim 6 , or a stereoisomer or salt thereof, wherein Y is H and R 3 is H or —C(O)R 5 .

9. The compound according to claim 6 , or a salt or stereoisomer thereof, wherein the optional double bond is present.

10. The compound according to claim 6 , or a stereoisomer or salt thereof, wherein R 2 is SH.

11. The compound according to claim 6 , or a stereoisomer or salt thereof, wherein Y is H and R 3 is H.

12. The compound according to claim 6 , or a stereoisomer or salt thereof, wherein R 1 is C 1-10 alkyl.

13. The compound according to claim 6 , or a stereoisomer or salt thereof, wherein R 1 is C 1-4 alkyl.

14. The compound according to claim 13 , or a stereoisomer or salt thereof, wherein R 2 is SH and n is 2.

15. The compound according to claim 14 , or a stereoisomer or salt thereof, wherein Y is H and R 3 is H.

16. The compound according to claim 15 , or a salt or stereoisomer thereof, wherein the optional double bond is present.

Assignees

• Uwm Res Foundation Inc

Inventors

• Cheng Yi-Qiang
• Hossain M Mahmun
• Steeber Douglas
• Frick Karyn
• Clark Steven
• Ulicki Joseph

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07C323/52

  the carbon skeleton being acyclic and saturated · CPC title

• C07K5/0606 Primary

  the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr · CPC title