[6,6] Fused bicyclic HDAC8 inhibitors

Patent metadata

Field	Value
Publication number	US-10370343-B2
Application number	US-201816003861-A
Country	US
Kind code	B2
Filing date	Jun 8, 2018
Priority date	Sep 3, 2015
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

The present invention is directed to compounds of Formula I:

and pharmaceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, or isomers or thereof, wherein R 1 , R 2 , R 2 ′, L, X, W, Y 1 , Y 2 , Y 3 , and Y 4 are described herein.

First claim

The invention claimed is:

1. A composition comprising a compound selected from:

or a pharmaceutically acceptable salt thereof.

2. The composition of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

3. The composition of claim 2 , further comprising the compound:

or a pharmaceutically acceptable salt thereof.

4. The composition of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

5. The composition of claim 4 , further comprising the compound:

or a pharmaceutically acceptable salt thereof.

6. A composition comprising a compound selected from:

or a pharmaceutically acceptable salt thereof,
wherein the compound is obtained by a process comprising a step of treating a compound:

with hydroxylamine and a first base to form a compound:

wherein R 1 is selected from the group consisting of:

7. The composition of claim 6 , wherein the first base comprises a hydroxide ion.

8. The composition of claim 7 , wherein the first base is NaOH.

9. The composition of claim 6 , wherein the process further comprises a step of treating a compound:

with R 1 —X′, wherein X′ is halogen, and a second base to form the compound:

10. The composition of claim 9 , wherein the second base is NaH, K 2 CO 3 , or Cs 2 CO 3 .

11. The composition of claim 9 , wherein X′ is Cl or Br.

12. The composition of claim 6 , wherein the composition comprises:

or a pharmaceutically acceptable salt thereof,
wherein the compound is obtained by a process, comprising the step of treating the compound:

with hydroxylamine and a first base to form the compound:

13. The composition of claim 12 , wherein the process further comprises the step of treating the compound:

with R 1 —X′, wherein X′ is halogen, and a second base to form the compound:

14. The composition of claim 6 , wherein the composition comprises:

or a pharmaceutically acceptable salt thereof,
wherein the compound is obtained by a process, comprising the step of treating the compound:

with hydroxylamine and a first base to form the compound:

15. The composition of claim 14 , wherein the process further comprises the step of treating the compound:

with R 1 —X′, wherein X′ is halogen, and a second base to form the compound:

16. A composition comprising a first compound selected from:

and
a second compound:

17. The composition of claim 16 , wherein the first compound is:

18. The composition of claim 16 , wherein the first compound is:

Assignees

• Forma Therapeutics Inc

Inventors

• Zheng Xiaozhang
• Ng Pui Yee
• Thomason Jennifer R
• Zablocki Mary-Margaret
• Han Bingsong
• Barczak Nicholas
• Liu Cuixian
• Rudnitskaya Aleksandra
• Lancia Jr David R
• Bair Kenneth W

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D265/36 Primary

  condensed with one six-membered ring · CPC title

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title