US 12,280,116 B2
ASGPR-binding compounds for the degradation of extracellular proteins
Mark George Saulnier, Higganum, CT (US); Jesse Jingyang Chen, Lexington, MA (US); Srinivasa Karra, Pembrooke, MA (US); Kevin Tyler Sprott, Needham, MA (US); Jason Allan Wiles, Madison, CT (US); and Soumya Ray, Quincy, MA (US)
Assigned to AVILAR THERAPEUTICS, INC., Waltham, MA (US)
Filed by AVILAR THERAPEUTICS, INC., Waltham, MA (US)
Filed on May 2, 2024, as Appl. No. 18/653,655.
Application 18/653,655 is a continuation of application No. 18/220,708, filed on Jul. 11, 2023, granted, now 12,076,408.
Application 18/220,708 is a continuation of application No. 17/877,538, filed on Jul. 29, 2022, granted, now 11,819,551, issued on Nov. 21, 2023.
Application 17/877,538 is a continuation of application No. PCT/US2021/015939, filed on Jan. 29, 2021.
Claims priority of provisional application 63/063,015, filed on Aug. 7, 2020.
Claims priority of provisional application 62/968,802, filed on Jan. 31, 2020.
Prior Publication US 2024/0307546 A1, Sep. 19, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/54 (2017.01); A61K 47/62 (2017.01); C07H 5/06 (2006.01); C07H 7/02 (2006.01); C07H 9/02 (2006.01); C07H 9/04 (2006.01); C07H 15/203 (2006.01); C07H 17/00 (2006.01); C07H 17/02 (2006.01); C07H 19/02 (2006.01); C07H 19/044 (2006.01); H03L 7/081 (2006.01); H03L 7/099 (2006.01)
CPC A61K 47/549 (2017.08) [A61K 47/62 (2017.08); C07H 5/06 (2013.01); C07H 7/02 (2013.01); C07H 9/02 (2013.01); C07H 9/04 (2013.01); C07H 15/203 (2013.01); C07H 17/00 (2013.01); C07H 17/02 (2013.01); C07H 19/02 (2013.01); C07H 19/044 (2013.01); H03L 7/0814 (2013.01); H03L 7/0818 (2013.01); H03L 7/0998 (2013.01)] 30 Claims
 
1. A method to treat a patient with an IgG mediated disorder comprising administering an effective amount of a compound of Formula:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
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;

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry
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.