ASGPR-binding compounds for the degradation of extracellular proteins

A method to treat a patient with an IgG mediated disorder comprising administering an effective amount of a compound of Formula:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, and haloalkyl;
• R5 is selected from the group consisting of hydrogen, alkyl, alkenyl, and haloalkyl;
• R2 is —NR6-heteroaryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of alkyl, alkenyl, haloalkyl, —OR6, F, Cl, —NR6R7, cyano, nitro, and C(O)R3;
• R3 at each occurrence is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, arylalkyl, alkenyl, aryl, heteroaryl, heterocycle, —OR8, and —NR8R9;
• R6 and R7 are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, alkenyl, aryl, haloalkyl, heteroaryl, heterocycle, and C(O)R3;
• R8 and R9 are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, alkenyl, aryl, heteroaryl, and heterocycle;
• LinkerA is bond;
• LinkerB is
• R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20 are independently at each occurrence selected from the group consisting of a bond, alkyl, —C(O)—, —C(O)O—, —OC(O)—, —C(O)NR6—, —NR6C(O)—, —NR6—, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, —[O—CH2C(O)]n—, and —[C(O)—CH2—O]n—, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21,
• n is independently selected at each instance from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
• R21 is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, F, Cl, hydroxyl, alkoxy, azide, amino, cyano, —NR6R7, —NR8SO2R3, —NR8S(O)R3, haloalkyl, aryl, heteroaryl, and heterocycle;
• LinkerC is selected from:
• R22 is selected from the group consisting of alkyl, —C(O)N—, —NC(O)—, —N—, —C(R21)—, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;
• LinkerD is selected from:
• R32 is selected from the group consisting of alkyl, N′X, —C-, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;
• X′ is an anionic group;
• and
• Extracellular Protein Targeting Ligand is an IgG Targeting Ligand that binds IgG, wherein the IgG Targeting Ligand is a peptide.