Granted Patent B2

US 12,729,193 · App. 18/134,985 · Granted Sep 8, 2026

Inventors: Christopher G. Nasveschuk (Stoneham, MA); James A Henderson (Weston, MA); Moses Moustakim (Cambridge, MA); Andrew Charles Good (Watertown, MA); David Proia (Newton, MA)

Assignee: C4 Therapeutics, Inc.

C07D401/14C07D401/04C07D405/14C07D471/04

Abstract

Claims (46)

1 . A compound of Formula:

or a pharmaceutically acceptable salt thereof;

wherein:

X is selected from the group consisting of a bond, alkyl, heterocycle, aryl, heteroaryl, bicycle, —NR 27 —, —NR 10 —, —CR 40 R 41 —, —O—, —C(O)—, —C(NR 27 )—, —C(S)—, —S(O)—, —S(O) 2 — and —S—; each of which is optionally substituted, as allowed by valence, to form a stable compound, with 1, 2, 3, or 4 substituents independently selected from R 40 ;

R 15 , R 16 , and R 17 are independently at each occurrence selected from the group consisting of a bond, alkyl, —C(O)—, —C(O)O—, —OC(O)—, —SO 2 —, —S(O)—, —C(S)—, —C(O)NR 27 —, —NR 27 C(O)—, —O—, —S—, —NR 27 —, —NR 10 —, —C(R 40 R 41 )—, bicycle, alkene, alkyne, haloalkyl, alkoxy, aryl, heterocycle, cycloalkyl, and heteroaryl; each of which is optionally substituted, as allowed by valence to form a stable compound, with 1, 2, 3, or 4 substituents independently selected from R 40 ; and wherein no more than two of R 15 , R 16 , and R 17 are selected to be bond;

R 18 is selected from the group consisting of hydrogen, halogen, cyano, —C(O)R 27 , —C(O)OR 27 , alkyl, —C(O)NR 10 R 27 , —NR 27 C(O)R 27 , —NR 10 R 27 , —OR 27 , —SR 27 , alkene, alkyne, haloalkyl, alkoxy, aryl, heterocycle, and heteroaryl; each of which is optionally substituted, as allowed by valence to form a stable compound, with 1, 2, 3, or 4 substituents independently selected from R 40 ;

R 27 is independently at each occurrence selected from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkene, alkyne, aryl, heteroaryl, heterocycle, and cycloalkyl;

R 40 is independently at each occurrence selected from the group consisting of hydrogen, cyano, nitro, alkyl, halogen, haloalkyl, —OR 10 , —SR 10 , —S(O)R 12 , —SO 2 R 12 , and —NR 10 R 11 ;

R 41 is aryl, heteroaryl, or hydrogen;

A is selected from the group consisting of:

n is 0, 1, or 2;

X 3 is NR 10 , NR 6′ , O, or S;

Q is CR 7 or N;

R 3 is hydrogen, alkyl, halogen, or haloalkyl;

or R 3 and R 6 are combined to form a 1 or 2 carbon attachment;

or R 3 and R 4 are combined to form a 1, 2, 3, or 4 carbon attachment;

or R 3 and an R 4 group adjacent to R 3 are combined to form a double bond;

R 4 and R 5 are independently selected from the group consisting of hydrogen, alkyl, halogen, haloalkyl, —OR 10 , —SR 10 , —S(O)R 12 , —SO 2 R 12 , and —NR 10 R 11 ;

R 6 and R 7 are independently selected from the group consisting of hydrogen, alkyl, halogen, haloalkyl, —OR 10 , —SR 10 , —S(O)R 12 , —SO 2 R 12 , and —NR 10 R 11 ;

R 6′ is hydrogen, alkyl, or haloalkyl;

or R 3 and R 6′ are combined to form a 1 or 2 carbon attachment;

each R 10 and R 11 are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, heterocycle, aryl, heteroaryl, —C(O)R 12 , —S(O)R 12 , and —SO 2 R 12 ;

each R 12 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, heterocycle, aryl, heteroaryl, —NR 13 R 14 , and OR 13 ; and

each instance of R 13 and R 14 is independently selected from the group consisting of hydrogen, alkyl, and haloalkyl.

2 . The compound of claim 1 , wherein the compound is selected from the group consisting of:

wherein Q 1 is N;

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 2 , wherein n is 1.

4 . The compound of claim 3 , wherein R 4 is hydrogen.

5 . The compound of claim 4 , wherein R 3 is hydrogen.

6 . The compound of claim 5 , wherein R 6 is hydrogen.

7 . The compound of claim 1 , wherein X is —C(O)—.

8 . The compound of claim 1 , wherein X is a bond.

9 . The compound of claim 6 , wherein R 15 is a bond, alkyl, haloalkyl, heterocycle, aryl, heteroaryl, or bicycle.

10 . The compound of claim 1 , wherein R 16 is a bond, alkyl, haloalkyl, heterocycle, aryl, heteroaryl, bicycle, —S(O) 2 —, —C(O)—, —C(O)O—, —OC(O)—, —O—, or —NR 10 —.

11 . The compound of claim 1 , wherein R 17 is a bond, alkyl, haloalkyl, heterocycle, aryl, heteroaryl, or bicycle.

12 . The compound of claim 6 , wherein R 18 is hydrogen, halogen, —C(O)R 27 , —C(O)OR 27 , —C(O)NR 10 R 27 , —N 27 C(O)R 27 , —NR 10 R 27 , or —OR 27 .

13 . The compound of claim 6 , wherein R 18 is aryl, heterocycle, or heteroaryl, each of which is optionally substituted, as allowed by valence to form a stable compound, with 1, 2, 3, or 4 substituents independently selected from R 40 .

14 . The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

15 . A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

16 . A method of treating a disorder mediated by cereblon, IKZF2, or IKZF4 in a human comprising administering an effective dose of a compound of claim 1 or a pharmaceutically acceptable salt or composition thereof to a human in need thereof.

17 . The method of claim 16 , wherein the disorder is a cancer or tumor.

18 . The method of claim 16 , wherein the disorder is an immune, autoimmune, or inflammatory disorder.

19 . The method of claim 16 , wherein the disorder is a hematological malignancy.

20 . The method of claim 16 , wherein the disorder is small cell lung carcinoma, non-small cell lung carcinoma, melanoma, breast cancer, triple negative breast cancer, multiple myeloma, leukemia, chronic myeloid leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, or a myelodysplastic syndrome.

Assignments (1)

Continuity (3)

References Cited (205)