Heterocyclic degronimers for target protein degradation

A method for treating a patient with abnormal cellular proliferation comprising administering an effective amount of a compound optionally in a pharmaceutically acceptable carrier, to a patient in need thereof, wherein the compound is of Formula:

• or a pharmaceutically acceptable salt thereof;
• wherein
• is selected from the group consisting of:
• A is CR8R9, C═O, C═S, C═CH2, SO2, S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl)2, P(O)alkyl, P(O)OH, or P(O)NH2;
• A′ is CR1R2, C═O, C═S, C═CH2, SO2, S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl)2, P(O)alkyl, P(O)OH, or P(O)NH2;
• A″ is CR3R4, C═O, C═S, C═CH2, SO2, S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl)2, P(O)alkyl, P(O)OH, or P(O)NH2;
• X is independently selected from the group consisting of NH, NR11, CH2, CHR12, C(R12)2, O, and S;
• Z is O, S, CH2, CH(C1-C4alkyl), or C(C1-C4alkyl)2;
• n is 0, 1, 2, 3, 4, or 5;
• is a single or double bond;
• R1, R2, R3, R4, R8, R9, and R13 are independently selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, amine, —NHalkyl, and —Nalkyl2;
• or R1 and R2 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 and O;
• or R3 and R4 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 and O;
• or R8 and R9 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 and O;
• or R13 and R5 form a 3, 4, 5, or 6 carbon fused ring wherein R5 is on the carbon alpha to R13 or a 1, 2, 3, or 4 carbon bridged ring wherein R5 is not on the carbon alpha to R13;
• R5 is selected at each instance from the group consisting of:
• alkyl, alkene, alkyne, halogen, 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;
• or two R5 substituents together with the carbon atom(s) to which they are bound can form a 3, 4, 5 or 6 membered ring;
• Q1, Q2, Q3 and Q4 are independently selected from the group consisting of CH, CR12, and N;
• and wherein no more than two of Q1, Q2, Q3, and Q4 are N;
• R11 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, C(O)H, —C(O)OH, —C(O)alkyl, and —C(O)Oalkyl;
• and
• R12 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, azide, amino, —C(O)H, —C(O)OH, —C(O)alkyl, —C(O)Oalkyl, —NHalkyl, —N(alkyl)2, —NHSO2alkyl, —N(alkyl)SO2alkyl, —NHSO2aryl, —N(alkyl)SO2aryl, —NHSO2alkenyl, —N(alkyl)SO2alkenyl, —NHSO2alkynyl, —N(alkyl)SO2alkynyl, cyano, nitro, nitroso, —SH, —Salkyl, and haloalkyl.