C3-carbon linked glutarimide Degronimers for target protein degradation

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• W1 is C═O;
• W2 is C═O;
• X is NH;
• n is 0 or 1;
• is a single or double bond;
• R6 is selected from:
• Y is independently selected from the group consisting of N, CH, and CR11, wherein 0, 1, or 2 instances of Y are selected to be N;
• Z is NH, O, S, or NR12;
• Z2 is NH or NR12;
• and when R10 is bonded to a Y that is carbon, then Y is CR10, and when R10 is bonded to a Z or Z2 that is nitrogen, then Z or Z2 is NR10;
• R15 is selected from the group consisting of hydrogen, alkyl, heterocyclic, carbocyclic, aryl, heteroaryl, hydroxyl, F, Cl, azide, CN-, alkoxy, amine, —NHalkyl, and —Nalkyl2;
• or R15 and R5 form a 3, 4, 5, or 6 carbon fused ring wherein R5 is on the carbon alpha to R15 or a 1, 2, 3, or 4 carbon bridged ring wherein R5 is not on the carbon alpha to R15;
• R5 is selected at each instance from the group consisting of alkyl, alkene, alkyne, heterocyclic, aryl, heteroaryl, halogen, hydroxyl, alkoxy, azide, amino, —NH (alkyl), —N(alkyl)2, —NHSO2(alkyl), —N(alkyl)SO2(alkyl), —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;
• R10 is -Linker-Targeting Ligand;
• R11 is selected at each instance from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, hydroxyl, heterocyclic, carbocyclic, alkoxy, aryl, heteroaryl, alkylamino, alkylhydroxyl, —NHalkyl, —Nalkyl2, amino, cyano, nitro, nitroso, sulfone, sulfoxide, thioalkyl, thiol, and haloalkyl;
• R12 is selected at each instance from the group consisting of hydrogen, alkyl, heterocyclic, heteroaryl, aryl, —C(O)H, —C(O)OH, —C(O)alkyl, —C(O)Oalkyl, —C(O)(aryl, —C(O)O(aryl), alkene, and alkyne;
• R13 and R14 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxy, amino, —NHalkyl, and —N(alkyl)2;
• or R13 and R14 together with the carbon atom to which they are attached, form C(O), C(S), C═CH2, 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;
• Linker is
• 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, alkene, haloalkyl, alkoxy, alkyne, aryl, heterocycle, heteroaryl, carbocycle, —C(O)—, —C(O)O—, —OC(O)—, —C(O)alkyl, —C(O)Oalkyl, —C(S)—, —SO2—, —S(O)—, —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-, -alkyl(R27)-alkyl(R28)—, —C(R27R28)—, —NHC(O)NH—, —N(R25)C(O)N(R25)—, and —N(H)C(O)N(R25)—, wherein each of R20, R21, R22, R23, and R24 is optionally substituted with one or two substituents selected from R101;
• 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, alkynyl, aryl, heteroaryl, and heterocyclic;
• R26 is hydrogen, alkyl, alkene, alkyne, aryl, heteroaryl, or heterocyclic;
• 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;
• R101 is independently selected at each occurrence from the group consisting of hydrogen, alkyl, alkene, alkyne, haloalkyl, alkoxy, hydroxyl, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy, CN, —COOalkyl, COOH, NO2, F, Cl, CF3, NH2, NHalkyl, and N(alkyl)2;
• and
• Targeting Ligand is a means for binding the Targeted Protein that mediates a disorder, wherein the Targeting Ligand is selected from those in FIGS. 1A through 8PPPPP.