N/O-linked degrons and degronimers for protein degradation

A compound of Formula:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• W1 is C═O;
• W2 is C═O;
• one X is NH and the other is CH2;
• n is 0, 1, 2, or 3;
• R1 is
• R2 is alkyl or hydrogen;
• R5 is selected at each instance from the group consisting of alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, azide, amino, cyano, —NH(alkyl), —N(alkyl)2, C(O)R4, haloalkyl, aryl, heteroaryl, and carbocyclic;
• R4 is selected at each instance from the group consisting of alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, azide, amino, —NHalkyl, —N(alkyl)2, —NHSO2alkyl, —N(alkyl)SO2alkyl, —NHSO2aryl, —N(alkyl)SO2aryl, —NHSO2alkenyl, —N(alkyl)SO2alkenyl, —NHSO2alkynyl, —N(alkyl)SO2alkynyl, and haloalkyl;
• R10 and R11 are hydrogen;
• R12 is Linker-H;
• Linker is selected from the group consisting of:
• wherein:
• X1 and X2 are independently selected from the group consisting of bond, NH, NR25, CH2, CHR25, C(R25)2, O, and S;
• R20, R21, R22, R23, and R24 are independently selected from the group consisting of bond, alkyl, —C(O)—, —C(O)O—, —OC(O)—, —C(O)alkyl, —C(O)Oalkyl, —SO2—, —S(O)—, —C(S)—, —C(O)NH—, —NHC(O)—, —N(alkyl)C(O)—, —C(O)N(alkyl)-, —O—, —S—, —NH—, —N(alkyl)-, —CH(—O—R26)—, —CH(—NHR25)—, —CH(—NH2)—, —CH(—NR252)—, —C(—O—R26)alkyl-, —C(—NHR25)alkyl-, —C(—NH2)alkyl-, —C(—NR252)alkyl-, —C(R4R4)—, -alkyl(R27)-alkyl (R28)—, —C(R27R28)—, —NHC(O)NH—, —N(R25)C(O)N(R25)—, —N(H)C(O)N(R25)—, alkenyl, haloalkyl, alkoxy, alkynyl, heteroarylalkyl, aryl, arylalkyl, heterocycle, heteroaryl, lactic acid, glycolic acid, carbocycle, —O—(CH2)1-12—O—, —NH—(CH2)1-12—NH—, —NH—(CH2)1-12—O—, —O—(CH2)1-12—NH—, —S—(CH2)1-12—O—, —O—(CH2)1-12—S—, —S—(CH2)1-12—S—, —S—(CH2)1-12—NH—, and —NH—(CH2)1-12—S—;
• each of which R20, R21, R22, R23, and R24 is optionally substituted with one or more substituents selected from R101,
• R101 is independently selected at each occurrence from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, hydroxyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocycloalkyl, aryloxy, heteroaryloxy, CN, —COOalkyl, COOH, NO2, F, Cl, Br, I, CF3, NH2, NHalkyl, and N(alkyl)2;
• R25 is selected at each instance from the group consisting of alkyl, —C(O) H, —C(O)OH, —C(O)alkyl, —C(O)Oalkyl, alkenyl, and alkynyl;
• R26 is hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, or alkynyl;
• and
• R27 and R28 are independently selected from the group consisting of hydrogen, alkyl, and amine, or together with the carbon atom to which they are attached, form C(O), C(S), C═CH2, a C3-C6 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;
• wherein:
• heteroaryl is a 5- or 6-membered aryl ring system that contains 1, 2, or 3 heteroatoms selected from the group consisting of O, N, and S;
• aryl is phenyl or naphthyl;
• and
• heterocycle is a monocyclic 3- to 8-membered heterocycle or a bicyclic 5- to 11-membered heterocycle, wherein heterocycle contains 1, 2, or 3 heteroatoms selected from the group consisting of O, N, and S.