Compounds and compositions for inhibition of FASN

Patent metadata

Field	Value
Publication number	US-10450286-B2
Application number	US-201916389286-A
Country	US
Kind code	B2
Filing date	Apr 19, 2019
Priority date	Mar 13, 2013
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

Abstract

The present invention relates to compounds and composition for inhibition of FASN, their synthesis, applications, and antidotes. An illustrative compound of the invention is shown below:

First claim

What is claimed is:

1. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein
R 1 is

A and B are each independently O;
L is

wherein m is 2, n is 1, and R b is C 1 -C 4 alkyl;
Ar 1 is a 6-member monocyclic aryl or 6-member monocyclic heteroaryl comprising 1 or 2 heteroatoms that are N, wherein said aryl or heteroaryl is either unsubstituted or optionally independently substituted with 1 or more substituents which can be the same or different and are independently selected from the group consisting of halogen, alkyl, and -alkoxy; and
R 2 is a substituted or unsubstituted 8-10 membered fused polycyclic aryl or heteroaryl, wherein R 2 is optionally substituted with 1 or more substituents which can be the same or different and are independently selected from the group consisting of halogen, alkyl and -alkoxy.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ar 1 is

wherein
Ph 1 is selected from the group consisting of phenyl, pyridinyl, pyrazinyl and pyrimidinyl; and
R e is selected from the group consisting of hydrogen, halogen and C 1 -C 3 alkyl.

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein Ph 1 is phenyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ar 1 is

wherein R e is selected from the group consisting of hydrogen, halogen and C 1 -C 3 alkyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R b is methyl.

6. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R b is methyl.

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R e is hydrogen.

8. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R e is halogen.

9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein Ar 1 is

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a substituted or unsubstituted 9-membered 6,5 bicyclic heteroaryl and said heteroaryl has 1, 2, 3, or 4 heteroatoms and said heteroatoms are independently O, S, or N.

11. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a substituted or unsubstituted 9-membered 6,5 bicyclic heteroaryl and said heteroaryl has 1, 2, 3, or 4 heteroatoms and said heteroatoms are independently O, S, or N.

12. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a substituted or unsubstituted 9-membered 6,5 bicyclic heteroaryl and said heteroaryl has 1, 2, 3, or 4 heteroatoms and said heteroatoms are independently O, S, or N.

13. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a substituted or unsubstituted 9-membered 6,5 bicyclic heteroaryl and said heteroaryl has 1, 2, 3, or 4 heteroatoms and said heteroatoms are independently O, S, or N.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from the group consisting of:

15. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from the group consisting of:

16. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein
R is

A and B are each independently O;
L is

substituted with one or more R b , wherein R b is methyl;
Ar 1 is

R e is selected from the group consisting of hydrogen, and halogen; and
R 2 is a substituted or unsubstituted 9-membered 6,5 bicyclic heteroaryl and said heteroaryl has 1, 2, 3, or 4 heteroatoms and said heteroatoms are independently O, S, or N, wherein R 2 is optionally substituted with 1 or more substituents which can be the same or different and are independently selected from the group consisting of halogen, alkyl and -alkoxy.

17. The compound of claim 16 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from the group consisting of:

18. The compound of claim 16 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from the group consisting of:

19. The compound of claim 16 , or a pharmaceutically acceptable salt thereof, wherein L is selected from the group consisting of:

20. The compound of claim 18 , or a pharmaceutically acceptable salt thereof, wherein L is selected from the group consisting of:

21. The compound of claim 16 , selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

22. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein
R 1 is

A and B are each independently O;
L is selected from the group consisting of:

Ar 1 is

R e is selected from the group consisting of hydrogen, and halogen; and
R 2 is selected from the group consisting of:

Assignees

• Forma Therapeutics Inc

Inventors

• Bair Kenneth W
• Lancia Jr David R
• Li Hongbin
• Loch James
• Lu Wei
• Martin Matthew W
• Millan David S
• Schiller Shawn E R
• Tebbe Mark J

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• C07D277/62

  Benzothiazoles · CPC title

• C07D217/16

  substituted by oxygen atoms · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title