GCN2 inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-10988477-B2
Application number	US-201916259979-A
Country	US
Kind code	B2
Filing date	Jan 28, 2019
Priority date	Jan 29, 2018
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

The present invention provides compounds inhibiting General amino acid Control Non-derepressible 2 kinase (“GCN2”), compositions thereof, and methods of using the same for treating various disorders, such as cancer.

First claim

We claim:

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
Ring A is a 4-8 membered saturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
Ring B is

Ring C is

each of R 1 is independently fluoro, methyl, ethyl, —OH, methoxy, —CH 2 OH,

each of R 2 is independently

R 3 is hydrogen;
R 4 is hydrogen;
m is 0, 1, 2, 3, 4 or 5;
n is 0, 1, or 2;
p is 0 or 1; and
q is 0 or 1.

2. The compound of claim 1 , of one of formula X-a, X-b, or X-c:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein m is 1, 2, 3, or 4.

4. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

5. The compound of claim 1 , wherein Ring A is:

6. The compound of claim 1 , wherein each of R 1 is independently fluoro, methyl, ethyl,

7. The compound of claim 1 , wherein each of R 1 is independently fluoro, methyl,

8. The compound of claim 1 wherein each of R 1 is independently fluoro, methyl,

9. The compound of claim 1 , wherein Ring A is

10. The compound of claim 1 , wherein each of R 2 is independently

11. The compound of claim 1 , wherein each of R 2 is independently —CHF 2 , —CF 3 , or —CF 2 CH 3 .

12. The compound of claim 1 , wherein Ring B is

13. The compound of claim 1 , wherein m is 3.

14. The compound of claim 1 , wherein n is 1.

15. The compound of claim 1 , wherein the compound is selected from the group consisting of:

Assignees

• Merck Patent Gmbh
• Vertex Pharma

Inventors

• Bayly Andrew
• Bleich Matthew
• Charrier Jean-Damien
• Dodd James
• Durrant Steven
• Eno Meredith Suzanne
• Etxebarria I Jardi Gorka
• Everitt Simon
• Fraysse Damien
• Kelly Shazia
• Knegtel Ronald
• Mochalkin Igor
• Mortimore Michael
• North Kiri
• Porichis Filippos
• Pullin Robert
• Rutherford Alistair
• Storck Pierre-Henri
• Twin Heather Clare
• Xiao Yufang

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title