ULK1 inhibitors and methods using same

Patent metadata

Field	Value
Publication number	US-10774092-B2
Application number	US-201916389784-A
Country	US
Kind code	B2
Filing date	Apr 19, 2019
Priority date	Aug 25, 2014
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

In certain aspects, the invention provides a method for treating a disease or condition in a subject, the method comprising co-administering to a subject in need thereof a therapeutically effective amount of at least one ULK1-inhibiting pyrimidine, and a therapeutically effective amount of an mTOR inhibitor.

First claim

What is claimed is:

1. A compound, or pharmaceutically acceptable salt thereof, having a structure of Formula A:

wherein:
R 10 is selected from the group consisting of: halogen; —OR 11 wherein R 11 is H, optionally substituted aryl, or optionally substituted heteroaryl; and NR 1 R 2 wherein R 1 is H or alkyl and R 2 is selected from the group consisting optionally substituted aryl and optionally substituted heteroaryl, wherein the aryl or heteroaryl of R 2 is optionally substituted with one or more substituent, wherein each substituent of the aryl or heteroaryl of R 2 is selected from the group consisting of alkyl, alkynyl, alkenyl, aryl, halide, nitro, amino, ester, ketone, aldehyde, hydroxy, carboxylic acid, and alkoxy;
R 4 is —O—(N-alkylbenzamide);
R 5 is selected from the group consisting of H, hydroxyl, optionally substituted alkyl, halo, optionally substituted alkoxy, or optionally substituted aryl, optionally substituted carboxyl, cyano, and nitro, or R 5 and R 6 together form a cyclic structure; and
R 6 is H or haloalkyl.

2. The compound of claim 1 , wherein R 6 is H.

3. The compound of claim 1 , wherein R 4 is —O—(N—(C 1 -C 6 )alkylbenzamide).

4. The compound of claim 1 , wherein R 4 is

5. The compound of claim 1 , wherein
R 10 is —N 1 R 2 ;
R 1 is H;
R 2 is selected from the group consisting of

and
R 6 is H.

6. The compound of claim 1 , wherein
R 10 is N 1 R 2 ;
R 1 is H;
R 2 is selected from the group consisting of

and
R 6 is H.

7. The compound of claim 1 , wherein R 10 is —NR 1 R 2 , wherein R 2 is an alkoxy-substituted phenyl.

8. The compound of claim 1 , wherein R 5 is selected from H, hydroxyl, optionally substituted alkyl, halo, optionally substituted alkoxy, or optionally substituted aryl.

9. The compound of claim 1 , wherein R 5 is optionally substituted alkyl.

10. The compound of claim 1 , wherein R 5 is Br.

11. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

12. A compound, or pharmaceutically acceptable salt thereof, having a structure of Formula A:

wherein:
R 10 is selected from the group consisting of: halogen; —OR 11 wherein R 11 is H, optionally substituted aryl, or optionally substituted heteroaryl; and —NR 1 R 2 wherein R 1 is H or alkyl and R 2 is selected from the group consisting of

R 4 is —NR 7 R 8 , wherein R 7 is H and R 8 is N-alkylbenzamide;
R 5 is selected from the group consisting of H, hydroxyl, optionally substituted alkyl, halo, optionally substituted alkoxy, or optionally substituted aryl, optionally substituted carboxyl, cyano, and nitro, or R 5 and R 6 together form a cyclic structure; and
R 6 is H or haloalkyl.

13. The compound of claim 12 , wherein R 6 is H.

14. The compound of claim 12 , wherein
R 10 is N 1 R 2 ;
R 1 is H;
R 2 is selected from the group consisting of

and
R 6 is H.

15. The compound of claim 12 , wherein
R 10 is N 1 R 2 ;
R 1 is H;
R 2 is selected from the group consisting of

and
R 6 is H.

16. The compound of claim 12 , wherein
R 10 is NR 1 R 2 ; and
R 2 is an alkoxy-substituted phenyl.

17. The compound of claim 12 , wherein R 5 is selected from H, hydroxyl, optionally substituted alkyl, halo, optionally substituted alkoxy, or optionally substituted aryl.

18. The compound of claim 17 , wherein R 5 is optionally substituted alkyl.

19. The compound of claim 17 , wherein R 5 is Br.

20. The compound of claim 17 , wherein R 5 is Cl.

Assignees

• Salk Inst For Biological Studi
• Sanford Burnham Prebys Medical Discovery Inst
• Univ Yale

Inventors

• Shaw Reuben J
• Egan Daniel F
• Cosford Nicholas
• Turk Benjamin
• Vamos Mitchell
• Panickar Dhanya Raveendra
• Chun Matthew
• Sheffler Douglas

Classifications

• C07D498/04 Primary

  Ortho-condensed systems · CPC title

• C07D239/47

  One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine · CPC title

• C07D239/42

  One nitrogen atom (nitro radicals C07D239/30) · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title