Bispecific degraders

1. A compound having a structure represented by formula (I):

wherein A represents A 1 :

wherein X and X 1 independently represent C or N, provided that one of X and X 1 represents N; wherein R 1 is absent if X 1 represents N, and if X 1 represents C, R 1 represents H, or wherein R 1 together with R 2 and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group;

R 2 represents H, halo, optionally substituted C1-C4 alkoxy, optionally substituted aryl, optionally substituted heteroaryl, or NR 6 R 7 , wherein each of R 6 and R 7 independently represents H or a substituent, or R 2 together with R 1 and the other atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group;

if X represents N, R 3 is absent, and if X represents C, R 3 independently represents H, halo, amine, optionally substituted amine, optionally substituted C1-C4 alkoxy, NR 6 R 7 , or , wherein L represents a linker,

wherein the linker is an alkylene chain or a polyethylene glycol chain, either of which may be interrupted by, and/or terminate (at either or both termini) in at least one of —O—, —S—, —N(R′)—, —C≡C—, —C(O)—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(NOR′)—, —C(O)N(R′)—, —C(O)N(R′)C(O)—, —C(O)N(R′)C(O)N(R′)—, —N(R′)C(O)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —OC(O)N(R′)—, —C(NR′)—, —N(R′)C(NR′)—, —C(NR′)N(R′)—, —N(R′)C(NR′)N(R′)—, —OB(Me)O—, —S(O) 2 —, —OS(O)—, —S(O)O—, —S(O)—, —OS(O) 2 —, —S(O) 2 O—, —N(R′)S(O) 2 —, —S(O) 2 N(R′)—, —N(R′)S(O)—, —S(O)N(R′)—, —N(R′)S(O) 2 N(R′)—, —N(R′)S(O)N(R′)—, C3-C12 carbocyclene, 3- to 12-membered heterocyclene, 5- to 12-membered heteroarylene or any combination thereof, wherein R′ is H or C1-C6 alkyl, wherein the interrupting and the one or both terminating groups may be the same or different, and

TL represents

or

 or wherein R 2 and R 3 , or R 3 and R 4 , together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group;

R 4 , and R 5 each independently represents H, halo, optionally substituted amine, optionally substituted C1-C4 alkoxy, optionally substituted aryl, optionally substituted heteroaryl, NR 6 R 7 , or , or wherein R 4 and R 5 , together with the atoms to which they are bound form an optionally substituted 5- or 6-membered carbocyclic group or an optionally substituted 5- or 6-membered heterocyclic group, provided that one of R 3 , R 4 and R 5 represents ;

or a pharmaceutically acceptable salt or stereoisomer thereof.

2. The compound of claim 1 , wherein R 3 represents , and the compound of formula (I) is represented by formula (Ia-1):

or a pharmaceutically acceptable salt or stereoisomer thereof.

3. The compound of claim 2 , wherein each of R 1 , R 2 , R 4 and R 5 represents H.

4. The compound of claim 1 , wherein R 4 is , and the compound of formula (I) is represented by formula (Ia-2):

or a pharmaceutically acceptable salt or stereoisomer thereof.

5. The compound of claim 4 , wherein each of R 1 , R 2 , R 3 and R 5 represents H.

6. The compound of claim 1 , wherein R 5 is , and the compound of formula (I) is represented by formula (Ia-3):

or a pharmaceutically acceptable salt or stereoisomer thereof.

7. The compound of claim 6 , wherein each of R 1 , R 2 , R 3 , and R 4 represents H.

8. The compound of claim 1 , wherein the targeting ligand has a structure of:

9. A compound which is

or a pharmaceutically acceptable salt or stereoisomer thereof.

10. A pharmaceutical composition, comprising a therapeutically effective amount of the compound of claim 1 or pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 , which is in the form of a capsule.

12. A method of treating a cancer characterized by aberrant bromodomain-containing protein 2 (BRD2), BRD3, or BRD4 activity, comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof.

13. The method of claim 12 , wherein the cancer is multiple myeloma.

14. The compound of claim 1 , wherein the targeting ligand has a structure of:

15. The compound of claim 1 , wherein the targeting ligand has a structure of:

16. The compound of claim 9 , which is

 or a pharmaceutically acceptable salt or stereoisomer thereof.

17. The compound of claim 9 , which is

or a pharmaceutically acceptable salt or stereoisomer thereof.

18. The compound of claim 9 , which is

or a pharmaceutically acceptable salt or stereoisomer thereof.

19. A pharmaceutical composition, comprising a therapeutically effective amount of the compound of claim 9 pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier.

20. A method of treating a cancer characterized by aberrant bromodomain-containing protein 2 (BRD2), BRD3, or BRD4 activity, comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 9 or a pharmaceutically acceptable salt or stereoisomer thereof.