US 12,441,740 B2
N/O-linked degrons and degronimers for protein degradation
Andrew J. Phillips, Littleton, CO (US); Christopher G. Nasveschuk, Stoneham, MA (US); James A. Henderson, Weston, MA (US); Yanke Liang, Belmont, MA (US); Minsheng He, Andover, MA (US); Martin Duplessis, Somerville, MA (US); and Chi-Li Chen, Newton, MA (US)
Assigned to C4 THERAPEUTICS, INC., Watertown, MA (US)
Filed by C4 THERAPEUTICS, INC., Watertown, MA (US)
Filed on Dec. 9, 2024, as Appl. No. 18/973,867.
Application 18/973,867 is a continuation of application No. 17/959,144, filed on Oct. 3, 2022, granted, now 12,180,225.
Application 17/959,144 is a continuation of application No. 16/721,650, filed on Dec. 19, 2019, granted, now 11,459,335, issued on Oct. 4, 2022.
Application 16/721,650 is a continuation of application No. PCT/US2018/038534, filed on Jun. 20, 2018.
Claims priority of provisional application 62/522,541, filed on Jun. 20, 2017.
Prior Publication US 2025/0101037 A1, Mar. 27, 2025
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 495/14 (2006.01); A61K 31/426 (2006.01); A61K 31/427 (2006.01); A61P 35/00 (2006.01); C07D 207/456 (2006.01); C07D 211/88 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 405/12 (2006.01); C07D 413/12 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); G07F 17/32 (2006.01)
CPC C07D 495/14 (2013.01) [C07D 207/456 (2013.01); C07D 211/88 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 405/12 (2013.01); C07D 413/12 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); G07F 17/3211 (2013.01); G07F 17/3225 (2013.01); G07F 17/3244 (2013.01); G07F 17/3246 (2013.01); G07F 17/3272 (2013.01); G07F 17/3288 (2013.01)] 19 Claims
 
1. A compound of Formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof;
wherein:
n is 0, 1, or 2;
R4 is selected at each instance from C1-6-alkyl, hydroxyl, C1-6-alkoxy, amino, —NHC1-6-alkyl, —N(C1-6-alkyl)2, and C1-6-haloalkyl;
R5 is selected at each instance from C1-6-alkyl, halogen, hydroxyl, C1-6-alkoxy, amino, cyano, —NH(C1-6-alkyl), —N(C1-6-alkyl)2, —C(O)R4, and C1-6-haloalkyl;
R12 is Linker-H;
Linker is selected from:

OG Complex Work Unit Chemistry
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;
X1 and X2 are independently selected from bond, NH, NR25, CH2, CHR25, C(R25)2, O, and S;
R20, R21, R23, and R24 are independently selected from bond, C1-6-alkyl, —C(O)—, —O—, —NH—, —N(C1-6-alkyl)-, C2-6-alkene, C1-6-haloalkyl, C2-6-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 R20, R21, R23, and R24 is optionally substituted with one substituent independently selected from R101;
R101 is independently selected at each occurrence from hydrogen, C1-6-alkyl, C1-6-haloalkyl, C1-6-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)OC1-6-alkyl, C(O)OH NO2, F, Cl, Br, NH2, NHC1-6-alkyl, and N(C1-6-alkyl)2; and
R25 is selected at each instance from C1-6-alkyl, —C(O)H, —C(O)OH, —C(O)C1-6-alkyl, and —C(O)OC1-6-alkyl.