Compounds for targeted degradation of BRD9
A BRD9 protein degrading compound of structure or a pharmaceutically acceptable salt thereof is provided for the treatment of a disorder mediated by BRD9, including but not limited to abnormal cellular proliferation including cancer.
1. A compound of Formula:
or a pharmaceutically acceptable salt thereof;
wherein:
Q 1 is independently at each occurrence selected from the group consisting of NH, N(alkyl), N(haloalkyl), CH 2 , O, and S;
X 3 is N, CH, or CR 3 ;
X 10 is C(R 7 ) 2 , C(O), or 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 ;
R 3 is independently at each occurrence selected from the group consisting of hydrogen, hydroxyl, alkoxy, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, cycloalkyl, fluorine, chlorine, bromine, and iodine;
each R 4 is independently selected from the group consisting of hydrogen, aryl, heteroaryl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkyl, fluorine, chlorine, bromine, and iodine;
each R 7 is independently hydrogen, methyl, or ethyl; and
R 8 is hydrogen, C 1 -C 4 alkyl, alkenyl, alkynyl, haloalkyl, or cycloalkyl.
2. A compound of structure
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
6. A compound of structure:
7. A compound of structure:
8. The compound of claim 6 , wherein the compound is
9. The compound of claim 6 , wherein the compound is
10. The compound of claim 6 , wherein the compound is