Granted Patent B2

US 12,570,626 · App. 18/079,815 · Granted Mar 10, 2026

Inventors: Andrew J. Phillips (Littleton, CO); Christopher G. Nasveschuk (Stoneham, MA); James A. Henderson (Weston, MA); Minsheng He (Andover, MA); Kiel Lazarski (Boston, MA)

Assignee: C4 Therapeutics, Inc.

C07D401/04C07D403/04C07D413/04

Abstract

Claims (53)

1 . A compound of Formula:

or a pharmaceutically acceptable salt thereof;

wherein:

W 1 is C═O;

W 2 is C═O;

R 2 is selected at each instance from the group consisting of hydrogen, alkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, —C(O)H, —C(O)OH, —C(O)alkyl, —C(O)Oalkyl, —C(O)(aryl or heteroaryl), —C(O)O(aryl or heteroaryl), alkene, and alkyne;

R 4 is selected from the group consisting of hydrogen, alkyl, and heterocyclic;

R 5 is selected at each instance from the group consisting of hydrogen, alkyl, alkene, alkyne, F, Cl, hydroxyl, alkylhydroxyl, alkoxy, azide, amino, alkylamino, cyano, —NH(alkyl), —N(alkyl) 2 , —NHSO 2 (alkyl), —N(alkyl)SO 2 alkyl, —NHSO 2 (aryl, heteroaryl, or heterocyclic), —N(alkyl)SO 2 (aryl, heteroaryl, or heterocyclic), —NHSO 2 alkenyl, —N(alkyl)SO 2 alkenyl, —NHSO 2 alkynyl, —N(alkyl)SO 2 alkynyl, haloalkyl, heteroalkyl, carbocyclic, C(O)R 40 , aryl, aryloxy, heterocyclo, heteroaryl, arylalkyl, O-arylalkyl, nitro, nitroso, sulfone, sulfoxide, thioalkyl, thiol, haloalkyl, and cycloalkyl;

R 10 and R 11 are independently selected from the group consisting of hydrogen, alkyl, carbocyclic, heterocyclic, aryl, heteroaryl, F, Cl, azide, cyano, hydroxyl, alkoxy, amine, —NH(alkyl), and —N(alkyl) 2 ;

or R 10 and R 11 together with the carbon to which they are bound form a 3-, 4-, 5-, or 6-membered spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N, O, and S;

R 13 and R 14 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxy, amino, —NHalkyl, and —N(alkyl) 2 ;

or R 13 and R 14 together with the carbon atom to which they are attached form C(O), C(S), C═CH 2 , a 3-, 4-, 5-, or 6-membered spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N and O;

R 16 is selected from the group consisting of:

or R 16 is a 4, 5, 6, 7, 8, 9, or 10 membered carbocyclo or aryl moiety, wherein the carbocyclo or aryl moiety is substituted with R 12 at any desired position; wherein the carbocyclo or aryl moiety is optionally further substituted with one, two, or three substituents selected from R 5 ; and wherein the carbocyclo or aryl moiety is attached through a carbon atom;

or R 16 is

 R 17 is selected from the group consisting of R 17a , R 17b , and R 17c ,

R 17a is selected from the group consisting of:

or R 17a is selected from the group consisting of

or R 17a is selected from the group consisting of:

R 17b is selected from the group consisting of:

or R 17b is —NR 2 aryl, —NR 2 heteroaryl, or NR 2 carbocycle, wherein the aryl, heteroaryl, and carbocycle moieties are substituted with a R 12 at any desired position, wherein the aryl, heteroaryl, and carbocycle moieties are optionally further substituted with one, two, or three substituents selected from R 5 ; and wherein the aryl, heteroaryl, and carbocycle moieties are optionally further substituted with one oxo group at a position allowed by valence;

R 17c is selected from the group consisting of:

or R 17c is —O-aryl, —O-heteroaryl, or —O-carbocycle, wherein the aryl, heteroaryl, and carbocycle moieties are substituted with a R 12 at any desired position, wherein the aryl, heteroaryl, and carbocycle moieties are optionally further substituted with one, two, or three substituents selected from R 5 ; and wherein the aryl, heteroaryl, and carbocycle moieties are optionally further substituted with one oxo group at a position allowed by valence;

R 40 is selected at each instance from the group consisting of: hydrogen, alkyl, alkene, alkyne, F, Cl, hydroxyl, alkoxy, azide, amino, cyano, —NH(alkyl), —N(alkyl) 2 , —NHSO 2 (alkyl), —N(alkyl)SO 2 alkyl, —NHSO 2 (aryl, heteroaryl or heterocyclic), —N(alkyl)SO 2 (aryl, heteroaryl or heterocyclic), —NHSO 2 alkenyl, —N(alkyl)SO 2 alkenyl, —NHSO 2 alkynyl, —N(alkyl) SO 2 alkynyl, haloalkyl, aryl, heteroaryl, heteroalkyl, heterocyclic, and carbocyclic;

is selected from the group consisting of a single and a double bond;

Y is independently selected from the group consisting of N, CH, and CR 5 ;

Z 1 is selected from the group consisting of CH 2 , CHR 2 , C(R 2 ) 2 , NR 2 , O, and S;

Z 2 is selected from the group consisting of NH, O, S, NR 2 , C=O, S=O, and SO 2 ;

wherein when R 12 is bonded to a Y, then Y is CR 12 ; when R 12 is bonded to a Z 1 that is nitrogen, then Z 1 is NR 12 ; when R 12 is bonded to Z 1 that is carbon, then Z 1 is CR 2 R 12 ; when R 12 is bonded to a Z 2 , then Z 2 is NR 12 ;

R 12 is -(Linker) A - Targeting Ligand;

(Linker) A is

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

R 20 , R 21 , R 22 , R 23 , and R 24 are independently selected from the group consisting of bond, alkyl, —C(O)—, —C(O)O—, —OC(O)—, —C(O) alkyl, —C(O)Oalkyl, —SO 2 -, —S(O)—, —C(S)-, —C(O)NH-, —NHC(O)—, —N(alkyl)C(O)—, —C(O)N(alkyl)-, —O—, —S—, —NH-, —N(alkyl)-, —CH(—O-R 26 )-, —CH(—NHR 2 )-, —CH(—NH 2 )-, —C(—O-R 26 ) alkyl-, —C(—NHR 2 )alkyl-, —C(R 40 R 40 )-, —alkyl(R 27 )-alkyl(R 28 )-, —C(R 27 R 28 )-, —NHC(O)NH-, —N(R 2 )C(O)N(R 2 )-, —N(H)C(O)N(R 2 )-, alkene, haloalkyl, alkoxy, alkyneheteroarylalkyl, aryl, arylalkyl, heterocycle, heteroaryl, and carbocycle;

each of which R 20 , R 21 , R 22 , R 23 , and R 24 is optionally substituted with one, two, or three substituents selected from R 101 ;

R 101 is independently selected at each occurrence from the group consisting of hydrogen, alkyl, alkene, alkyne, haloalkyl, alkoxy, hydroxyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocycloalkyl, aryloxy, heteroaryloxy, CN, —COOalkyl, COOH, NO 2 , F, Cl, CF 3 , NH 2 , NHalkyl, and N(alkyl) 2 ;

R 26 is selected from the group consisting of hydrogen, alkyl, silane, arylalkyl, heteroarylalkyl, alkene, alkyne, aryl, heteroaryl, and heterocyclic;

R 27 and R 28 are independently selected from the group consisting of hydrogen, alkyl, amine, or together with the carbon atom to which they are attached, form C(O), C(S), C═CH 2 , a C 3 -C 6 spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N and O, or form a 1 or 2 carbon bridged ring; and

Targeting Ligand is a means for binding a Target Protein that mediates a disease.

2 . The compound of claim 1 , wherein R 2 is hydrogen.

3 . The compound of claim 1 , wherein R 4 is hydrogen.

4 . The compound of claim 1 , wherein R 10 and R 11 are both hydrogen.

5 . The compound of claim 1 , wherein R 13 and R 14 are both hydrogen.

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

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

8 . The compound of claim 1 , wherein R 17 is

9 . The compound of claim 1 , wherein R 17 is

10 . The compound of claim 1 , wherein R 17 is

11 . The compound of claim 1 , wherein R 17 is selected from the group consisting of:

12 . The compound of claim 1 , wherein the Target Protein is the androgen receptor.

13 . The compound of claim 1 , wherein the Target Protein is the estrogen receptor.

14 . A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

15 . A method for treating a human with a medical disorder comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, wherein the medical disorder is a cancer mediated by the Target Protein.

16 . The method of claim 15 , wherein the cancer is selected from the group consisting of colon cancer, prostate cancer, breast cancer, and testicular cancer.

Assignments (1)

Continuity (4)

References Cited (257)