Compounds for targeted degradation of BRD9
BRD9 protein degradation compounds or pharmaceutically acceptable salts thereof are provided for the treatment of disorders mediated by BRD9, including but not limited to abnormal cellular proliferation.
1. A compound of Formula:
or a pharmaceutically acceptable salt thereof;
wherein:
Q 1 is NH or O;
X 3 is N, CH, or CR 3 ;
X 10 is CH 2 or C(O);
X 11 is heterocycle optionally substituted with 1, 2, or 3 groups independently selected from R 3 ;
X 16 is selected from the group consisting of N, CH, and CR 4 ;
each R 3 is independently selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, fluorine, and chlorine;
each R 4 is independently selected from the group consisting of hydrogen, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, fluorine, and chlorine;
each R 7 is independently hydrogen, methyl, or ethyl; and
R 8 is C 1 -C 4 alkyl or C 2 -C 4 alkenyl.
2. The compound of claim 1 , wherein X 11 is selected from the group consisting of:
3. The compound of claim 1 , wherein Q 1 is NH.
4. The compound of claim 3 , wherein X 10 is CH 2 .
5. The compound of claim 4 , wherein each R 7 is CH 3 .
6. The compound of claim 5 , wherein each R 4 is OCH 3 .
7. The compound of claim 6 , wherein X 11 is selected from the group consisting of:
8. The compound of claim 1 , wherein the compound is of Formula:
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 8 , wherein Q 1 is NH.
10. The compound of claim 8 , wherein X 10 is CH 2 .
11. The compound of claim 10 , wherein each R 7 is CH 3 .
12. The compound of claim 11 , wherein X 11 is selected from the group consisting of:
13. The compound of claim 1 , wherein the compound is of Formula:
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 13 , wherein each R 7 is CH 3 .
15. The compound of claim 1 , wherein the compound is of Formula:
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 1 , wherein the compound is of Formula:
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 16 , wherein X 11 is selected from the group consisting of:
18. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutical salt thereof and a pharmaceutically acceptable excipient.
20. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is formulated for oral administration.
21. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition is a tablet or capsule.
22. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is formulated for parenteral administration.
23. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is formulated for intravenous administration.