US 9,938,302 B2 · Chimeric compounds targeting proteins, compositions, methods, and uses thereof

Abstract

The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.

Claims26

Dependent claims

A compound of Formula (I):

or a pharmaceutically acceptable salt or solvate thereof, wherein:
R1 is hydroxyl, halogen, nitro, optionally substituted amino, optionally substituted C1 to C6 alkoxy, optionally substituted C1 to C6 alkyl, optionally substituted C2 to C6 alkenyl, optionally substituted C3 to C8 carbocyclyl, or optionally substituted C3 to C8 heterocyclyl;
R2, R3, and R4, are each independently H, deuterium, hydroxyl, halogen, nitro, optionally substituted amino, optionally substituted C1 to C6 alkoxy, optionally substituted C1 to C6 alkyl, optionally substituted C2 to C6 alkenyl, optionally substituted C3 to C8 carbocyclyl, or optionally substituted C3 to C8 heterocyclyl;
or,
R1 is H and R2 is hydroxyl, halogen, nitro, optionally substituted amino, optionally substituted C1 to C6 alkoxy, optionally substituted C1 to C6 alkyl, optionally substituted C2 to C6 alkenyl, optionally substituted C3 to C8 carbocyclyl, or optionally substituted C3 to C8 heterocyclyl;
each R5 is independently H, deuterium, or optionally substituted C1 to C6 alkyl;
X is CH2 or C═O;
Q is C═O or SO2;
and
n is or 2.

7 more elements

Dependencies are inferred from the claim text.

Chimeric compounds targeting proteins, compositions, methods, and uses thereof

Life of this patent

Chimeric compounds targeting proteins, compositions, methods, and uses thereof

Life of this patent

Abstract

Claims26