ULK1 inhibitors and methods using same
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.
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.