Heterocyclic degronimers for target protein degradation

A compound of Formula:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• A is CR8R9, C=O, C=S, or C═CH2;
• A′ is C═O, C=S, C═CH2, SO2, or S(O);
• A″ is CR3R4, C═O, C=S, C═CH2, SO2, or S(O);
• X is independently selected from NH and NR11;
• Z is O, S, CH2, CH(C1-C4alkyl), or C(C1-C4alkyl)2;
• n is 0, 1, 2, 3, 4, or 5;
• m is 1 or 3;
• is a single or double bond;
• R3, R4, R6, R7, R8, R9, and R13 are independently selected from hydrogen, alkyl, hydroxyl, alkoxy, amine, —NHalkyl, and —Nalkyl2;
• or R3 and R4 form a 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 R3 and R7 form a 1 or 2 carbon bridged ring;
• or R13 and R4 form a 1 or 2 carbon bridged ring;
• 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:
• 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 membered ring:
• Q1, Q2, Q3, and Q4 are independently selected from CH, CR12, and N;
• and wherein no more than two of Q1, Q2, Q3, and Q4 are N;
• R11 is independently selected from alkyl, alkenyl, alkynyl, C(O)H, —C(O)OH, —C(O)alkyl, and —C(O)Oalkyl;
• and
• R12 is independently selected from 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;
• wherein for compounds of Formula IV and Formula V at least one of:
• a, b, c, d, or e is satisfied:
• a. R3 and R4 form a 4, 5, or 6 membered spiroheterocycle or 4, 5, or 6 membered spirocarbocycle;
• b. R8 and R9 form a 4, 5, or 6 membered spiroheterocycle or 3, 4, 5, or 6 membered spirocarbocycle;
• c. R4 and R13 form a 1 or 2 carbon bridged ring;
• d. A′ is SO2 or S(O);
• or
• e. A″ is SO2 or S(O);
• and
• wherein for compounds of Formula VI at least one of:
• f, g, h, i, j, k, l, or m is satisfied:
• f. m is 3 and n is not 0;
• g. R3 and R4 form a spirocycle;
• h. R8 and R9 form a spirocycle;
• i. R4 and R13 form a 1 or 2 carbon bridged ring;
• j. R13 and R5 form a 3, 4, 5, or 6 carbon fused ring;
• k. R13 and R5 form a 1 or 2 carbon bridged ring;
• l. A′ is SO2 or S(O);
• or
• m. A″ is SO2 or S(O).