Heterocyclic compounds as modulators of beta-catenin / TCF4 interaction
Provided herein are compounds that are useful for or methods of inhibiting β-catenin or disrupting the interaction between β-catenin and T-cell factor 4, which are useful in the treatment of diseases or health conditions, such as cancer, neurodegenerative, a metabolic disease, a cardiovascular disease, fibrosis, and a bone disease. In one aspect, the compounds have Formula 1 wherein R 1 is —(CR 4 2 ) m XR 5 ; R 2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aralkyl, heteroaralkyl, or heteroaryl; and R 3 is —(CR 6 2 ) n R 7 .
1 . A method of inhibiting β-cat or disrupting the interaction between β-cat and TCF4, the method comprising:
contacting β-cat with a compound selected from the group consisting of:
or
a pharmaceutically acceptable salt thereof.
2 . A method of treating cancer in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound selected from the group consisting of:
a pharmaceutically acceptable salt thereof.
3 . The method of claim 2 , wherein the cancer is selected from the group consisting of colorectal cancer, hepatocellular cancer, melanoma, liver cancer, breast cancer, prostate cancer, and leukemia.