3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

1. A compound of Formula (Ic):

or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof,

wherein:

each R 1 is independently (C 1 -C 6 )alkyl;

R 2 is (C 1 -C 6 )alkyl substituted with one to three R 4 ;

each R 4 is independently selected from phenyl or 5- or 6-membered heteroaryl comprising 1 to 4 heteroatoms selected from O, N, and S, wherein the phenyl and heteroaryl groups are optionally substituted with one to three R 7 ;

each R 7 is independently selected from (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 9 , —NR 8 C(O)R 9 , (C 1 -C 6 )hydroxyalkyl, halogen, —OH, —NH 2 , CN, (C 6 -C 10 )aryl, 5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, (C 3 -C 7 )cycloalkyl, and 5- to 7-membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from O, N, and S, or

two R 7 , when on adjacent atoms, together with the atoms to which they are attached form a (C 6 -C 10 )aryl ring or a 5- or 6-membered heteroaryl ring comprising 1 to 3 heteroatoms selected from O, N, and S, optionally substituted with one or more R 10 , or

two R 7 , when on adjacent atoms, together with the atoms to which they are attached form a (C 5 -C 7 )cycloalkyl ring or a 5- to 7-membered heterocycloalkyl ring comprising 1 to 3 heteroatoms selected from O, N, and S, optionally substituted with one or more R 10 ;

R 8 and R 9 are each independently H or (C 1 -C 6 )alkyl;

each R 10 is independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, (C 1 -C 6 )hydroxyalkyl, halogen, —OH, —NH 2 , and CN; and

q is 0.

2. The compound according to claim 1 , wherein R 4 is phenyl substituted with one to three R 7 .

3. The compound according to claim 1 , wherein R 4 is 5-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, are optionally substituted with one to three R 7 .

4. The compound according to claim 1 , wherein R 4 is 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, optionally substituted with one to three R 7 .

5. The compound according to claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

7. The pharmaceutical composition of claim 6 further comprising at least one additional pharmaceutical agent.

8. A method of degrading IKZF2 comprising administering to the patient in need thereof a compound according to claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

9. A method of treating a disease or disorder that is affected by the modulation of IKZF2 protein levels comprising administering to the patient in need thereof a compound according to claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

10. A method of modulating IKZF2 protein levels comprising administering to the patient in need thereof a compound according to claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

11. A method of reducing the proliferation of a cell the method comprising, contacting the cell with a compound according to claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and reducing IKZF2 protein levels.

12. A pharmaceutical composition comprising a therapeutically effective amount of a compound selected from:

or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

13. The pharmaceutical composition of claim 12 further comprising at least one additional pharmaceutical agent.

14. A method of treating an IKZF2-dependent cancer comprising administering to the patient in need thereof a compound selected from:

or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

15. The method of claim 14 , wherein the cancer is selected from non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal cancer (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, carcinoid, and gastrointestinal stromal tumor (GIST).

16. The method of claim 14 , wherein the cancer is a cancer for which the immune response is deficient or an immunogenic cancer.