Granted Patent B2

US 12,441,740 · App. 18/973,867 · Granted Oct 14, 2025

Inventors: Andrew J. Phillips (Littleton, CO); Christopher G. Nasveschuk (Stoneham, MA); James A. Henderson (Weston, MA); Yanke Liang (Belmont, MA); Minsheng He (Andover, MA); Martin Duplessis (Somerville, MA); Chi-Li Chen (Newton, MA)

Assignee: C4 THERAPEUTICS, INC.

C07D495/14C07D207/456C07D211/88C07D401/12C07D401/14C07D403/04C07D405/12C07D413/12C07D471/04C07D487/04G07F17/3211G07F17/3225G07F17/3244G07F17/3246G07F17/3272G07F17/3288

Abstract

Claims (37)

1. A compound of Formula:

or a pharmaceutically acceptable salt thereof;

wherein:

n is 0, 1, or 2;

R 4 is selected at each instance from C 1-6 -alkyl, hydroxyl, C 1-6 -alkoxy, amino, —NHC 1-6 -alkyl, —N(C 1-6 -alkyl) 2 , and C 1-6 -haloalkyl;

R 5 is selected at each instance from C 1-6 -alkyl, halogen, hydroxyl, C 1-6 -alkoxy, amino, cyano, —NH(C 1-6 -alkyl), —N(C 1-6 -alkyl) 2 , —C(O)R 4 , and C 1-6 -haloalkyl;

R 12 is Linker-H;

Linker is selected from:

wherein:

Heteroaryl is a 5- or 6-membered heteroaryl containing 1 or 2 heteroatoms selected from nitrogen, oxygen, and sulfur;

Aryl is phenyl;

Heterocycle is a 4- to 6-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, or 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms;

X 1 and X 2 are independently selected from bond, NH, NR 25 , CH 2 , CHR 25 , C(R 25 ) 2 , O, and S;

R 20 , R 21 , R 23 , and R 24 are independently selected from bond, C 1-6 -alkyl, —C(O)—, —O—, —NH—, —N(C 1-6 -alkyl)-, C 2-6 -alkene, C 1-6 -haloalkyl, C 2-6 -alkyne, phenyl, 4- to 6-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, or 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, and 5- or 6-membered heteroaryl;

each of which R 20 , R 21 , R 23 , and R 24 is optionally substituted with one substituent independently selected from R 101 ;

R 101 is independently selected at each occurrence from hydrogen, C 1-6 -alkyl, C 1-6 -haloalkyl, C 1-6 -alkoxy, hydroxyl, phenyl, 5- or 6-membered heteroaryl, 4- to 6-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, or 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, CN, —C(O)OC 1-6 -alkyl, C(O)OH NO 2 , F, Cl, Br, NH 2 , NHC 1-6 -alkyl, and N(C 1-6 -alkyl) 2 ; and

R 25 is selected at each instance from C 1-6 -alkyl, —C(O)H, —C(O)OH, —C(O)C 1-6 -alkyl, and —C(O)OC 1-6 -alkyl.

2. The compound of claim 1 , wherein R 20 , R 21 , R 23 , and R 24 are independently selected from bond, C 1-6 -alkyl, —C(O)—, —O—, —NH—, —N(C 1-6 -alkyl)-, phenyl, and 4- to 6-membered heterocycle containing 1 or 2 nitrogen atoms.

3. The compound of claim 1 , wherein the Linker is

4. The compound of claim 1 , wherein the Linker is

5. The compound of claim 1 , wherein the Linker is

6. The compound of claim 1 , wherein R 20 , R 21 , R 23 , and R 24 are not substituted.

7. The compound of claim 1 , wherein n is 0.

8. The compound of claim 1 , wherein heterocycle is piperidinyl or piperazinyl.

9. The compound of claim 1 , wherein at least one R 5 is F.

10. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 10 , wherein the Linker is

12. The compound of claim 10 , wherein the Linker is

13. The compound of claim 10 , wherein the Linker is

14. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

16. A method for the treatment of a hematopoietic malignancy disorder comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof to a patent in need thereof, wherein the hematopoietic malignancy disorder can be treated by modulating the function or activity of cereblon-containing E3 ubiquitin ligase protein complex.

17. The method of claim 16 , wherein the hematopoietic malignancy disorder is mediated by Ikaros or Aiolos.

18. The method of claim 16 , wherein the hematopoietic malignancy disorder is acute myelogenous leukemia or lymphoblastic leukemia.

19. The method of claim 16 , wherein the hematopoietic malignancy disorder is multiple myeloma.

Assignments (1)

Continuity (5)

References Cited (236)