Phenyl and pyridinyl hydroxamic acids

Patent metadata

Field	Value
Publication number	US-10370324-B2
Application number	US-201715807782-A
Country	US
Kind code	B2
Filing date	Nov 9, 2017
Priority date	Nov 10, 2016
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

The present invention relates to pyrimidine hydroxy amide compounds, the use of such compounds in the inhibition of HDAC6, and the use of such compounds in the treatment of various diseases, disorders, or conditions related to HDAC6.

First claim

The invention claimed is:

1. The compound of Formula I:

or a pharmaceutically acceptable salt thereof;
wherein
R is N;
R 1 is H or C 1 -C 3 alkyl;
R 2 and R 3 are H; or
R 2 is H and R 3 is phenyl, wherein the phenyl ring is optionally and independently substituted with 1, 2, or 3 halo, C 1 -C 6 alkyl or C 1 -C 6 alkoxy groups; or
R 2 and R 3 are taken together to form a C 3 -C 6 cycloalkyl ring or a C 2 -C 5 heterocycloalkyl ring; and
R 4 is phenyl, wherein the phenyl ring is optionally and independently substituted with 1, 2, or 3 halo, C 1 -C 6 alkyl or C 1 -C 6 alkoxy groups.

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

3. The compound of claim 1 , wherein
R 2 is H and R 3 is phenyl, wherein the phenyl ring is optionally and independently substituted with 1, 2, or 3 halo, C 1 -C 6 alkyl or C 1 -C 6 alkoxy groups; and
R 4 is phenyl, wherein the phenyl ring is optionally and independently substituted with 1, 2, or 3 halo, C 1 -C 6 alkyl or C 1 -C 6 alkoxy groups.

4. The compound of claim 3 , wherein the compound of Formula I is:

or a pharmaceutically acceptable salt thereof.

5. A compound selected from the group consisting of:

or pharmaceutically acceptable salts thereof.

6. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.

7. A compound of Formula Ia:

or a pharmaceutically acceptable salt thereof;
wherein
R is C(H);
R 1 is H or C 1 -C 3 alkyl;
R 2 and R 3 are H; or
R 2 and R 3 are taken together to form a C 3 -C 6 cycloalkyl ring or a C 2 -C 5 heterocycloalkyl ring; and
R 4 is phenyl, wherein the phenyl ring is optionally and independently substituted with 1, 2, or 3 halo, C 1 -C 6 alkyl or C 1 -C 6 alkoxy groups.

8. The compound of claim 7 , wherein
R 1 is H;
R 2 and R 3 are H;
R 4 is phenyl, wherein the phenyl ring is optionally and independently substituted with 1, 2, or 3 halo, C 1 -C 6 alkyl or C 1 -C 6 alkoxy groups.

9. The compound of claim 7 , wherein
R 4 is phenyl, wherein the phenyl ring is optionally and independently substituted with 1, 2, or 3 halo or C 1 -C 6 alkoxy groups.

10. The compound of claim 7 , wherein the compound of Formula Ia is:

or a pharmaceutically acceptable salt thereof.

Assignees

• Acetylon Pharmaceuticals Inc

Inventors

• Van Duzer John H
• Mazitschek Ralph

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07C259/10 Primary

  having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• C07D309/14

  Nitrogen atoms not forming part of a nitro radical · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title