IP Library › Granted Patent US 12,371,442
Granted Patent B2
US 12,371,442 · App. 18/144,800 · Granted Jul 29, 2025

Isoindolinone and indazole compounds for the degradation of EGFR

Inventors: Christopher G. Nasveschuk (Stoneham, MA); Martin Duplessis (Somerville, MA); Jae Young Ahn (Somerville, MA); Alexander W. Hird (Belmont, MA); Ryan E. Michael (Erie, CO); Kiel Lazarski (Boston, MA); Yanke Liang (Belmont, MA); Georg Jaeschke (Basel, CH); Antonio Ricci (Biel-Benken, CH); Annick Goergler (Colmar, FR); Daniel Rueher (Raedersdorf, FR)
Assignee: C4 Therapeutics, Inc.
C07D519/00A61K9/009A61K9/02A61K9/08A61K9/2013A61K9/2018A61K9/2054A61K9/4825A61K9/485A61K9/4858A61K9/4866A61K47/10A61K47/12A61K47/26A61K47/32A61K47/38C07D487/04
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Quick Facts
Patent No.
US 12,371,442
App. No.
18/144,800
Granted
Jul 29, 2025
Kind
B2
Abstract

The invention provides compounds that degrade the epidermal growth factor receptor (EGFR) including mutant forms via the ubiquitination of the EGFR protein and subsequent proteasomal degradation. The compounds are useful for the treatment of various cancers.

Claims (38)

1. A method of treating an EGFR mediated cancer comprising administering an effective amount of a compound of Formula:

or a pharmaceutically acceptable salt thereof to a human in need thereof,

wherein:

y is 0, 1, 2, or 3;

B* is heteroaryl or aryl optionally substituted with 1, 2, or 3 R 31 substituents;

R 31 is independently selected at each occurrence from the group consisting of hydrogen, F, Cl, Br, I, C 1-6 -alkyl, cyano, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, C 3-8 -cycloalkyl, and halo-C 3-8 -cycloalkyl and can be located on either ring where present on a bicycle;

R 32 is hydrogen, F, Cl, Br, I, C 1-6 -alkyl, halo-C 1-6 -alkyl, C 3-8 -cycloalkyl, or halo-C 3-8 -cycloalkyl; and

R 33 is hydrogen, F, Cl, Br, I, C 1-6 -alkyl, halo-C 1-6 -alkyl, C 3-8 -cycloalkyl, or halo-C 3-8 -cycloalkyl and can be located on the dihydropyrrole or imidazole ring.

2. The method of claim 1 , wherein B* is

3. The method of claim 2 , wherein y is 1.

4. The method of claim 3 , wherein R 31 is selected from the group consisting of hydrogen, F, C 1-6 -alkyl, cyano, C 1-6 -alkoxy, and halo-C 1-6 -alkyl.

5. The method of claim 3 , wherein R 31 is F.

6. The method of claim 5 , wherein R 32 is hydrogen.

7. The method of claim 6 , wherein R 33 is hydrogen.

8. The method of claim 1 , wherein B* is

9. The method of claim 8 , wherein R 31 is selected from the group consisting of hydrogen, F, C 1-6 -alkyl, cyano, C 1-6 -alkoxy, and halo-C 1-6 -alkyl.

10. The method of claim 9 , wherein R 32 is hydrogen.

11. The method of claim 10 , wherein R 33 is hydrogen.

12. The method of claim 1 , wherein R 32 is hydrogen.

13. The method of claim 12 , wherein B* is

14. The method of claim 13 , wherein y is 1.

15. The method of claim 1 , wherein R 33 is hydrogen.

16. The method of claim 15 , wherein B* is

17. The method of claim 16 , wherein y is 1.

18. The method of claim 1 , wherein the compound is of structure:

or a pharmaceutically acceptable salt thereof.

19. The method of claim 1 , wherein the compound is of structure:

or a pharmaceutically acceptable salt thereof.

20. The method of claim 1 , wherein the compound is of structure:

or a pharmaceutically acceptable salt thereof.

21. The method of claim 1 , wherein the compound is administered orally.

22. The method of claim 19 , wherein the compound is administered orally.

23. The method of claim 1 , wherein the EGFR mediated cancer is selected from the group consisting of colon cancer, rectal cancer, lung cancer, breast cancer, head and neck cancer, glioblastoma, pancreatic cancer, thyroid cancer, astrocytoma, esophageal cancer, cervical cancer, synovial sarcoma, ovarian cancer, liver cancer, bladder cancer, and kidney cancer.

24. The method of claim 1 , wherein the EGFR mediated cancer is a non-small-cell lung cancer.

25. The method of claim 1 , wherein the EGFR mediated cancer is a small-cell lung cancer.

26. The method of claim 19 , wherein the EGFR mediated cancer is selected from the group consisting of colon cancer, rectal cancer, lung cancer, breast cancer, head and neck cancer, glioblastoma, pancreatic cancer, thyroid cancer, astrocytoma, esophageal cancer, cervical cancer, synovial sarcoma, ovarian cancer, liver cancer, bladder cancer, and kidney cancer.

27. The method of claim 19 , wherein the EGFR mediated cancer is a non-small-cell lung cancer.

28. The method of claim 19 , wherein the EGFR mediated cancer is a small-cell lung cancer.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2025
From: NASVESCHUK, CHRISTOPHER G.; AHN, JAE YOUNG; DUPLESSIS, MARTIN; HIRD, ALEXANDER W.; MICHAEL, RYAN E.; LAZARSKI, KIEL; LIANG, YANKE
To: C4 THERAPEUTICS, INC.
Reel/Frame 070248/0636 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2025
From: JAESCHKE, GEORG; RICCI, ANTONIO; GOERGLER, ANNICK; RUEHER, DANIEL
To: F. HOFFMAN-LA ROCHE AG
Reel/Frame 070248/0647 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2025
From: F. HOFFMAN-LA ROCHE AG
To: HOFFMAN-LA ROCHE INC.
Reel/Frame 070248/0656 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2025
From: HOFFMAN-LA ROCHE INC.
To: C4 THERAPEUTICS, INC.
Reel/Frame 070248/0662 →
Continuity (5)
Continuation 17843769 · Jun 17, 2022
Continuation PCTUS2020066211 · Dec 18, 2020
Provisional Application 62951464 · Dec 20, 2019
Provisional Application 62951467 · Dec 20, 2019
Related Publication 20240076300A1 · Mar 7, 2024
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