Heterocyclic compounds as modulators of beta-catenin/TCF4 interaction

Abstract

Provided herein are compounds useful for inhibiting beta-catenin or disrupting the interaction between beta-catenin and T cytokine 4, or methods of inhibiting beta-catenin or disrupting the interaction between beta-catenin and T cytokine 4, which are useful for the treatment of diseases or health conditions, such as cancer, neurodegenerative diseases, metabolic diseases, cardiovascular diseases, fibrosis and bone diseases. In one aspect, the compounds have Formula 1: wherein R1 is-(CR42) mXR5; r2 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclic alkenyl, aryl, aralkyl, heteroaralkyl or heteroaryl; and R3 is-(CR62) nR7.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to Singapore Patent Application No. 10201908175Q filed 4 September 2019, the entire contents of which are hereby incorporated by reference. technical field [0003] The present disclosure generally relates to methods of inhibiting the Wnt / β-catenin (β-cat) signaling pathway. More specifically, the present disclosure provides small molecule inhibitors of β-cat / T cell factor (TCF4), an interaction that results in attenuation of downstream Wnt expression. The compounds and methods provided herein are useful for treating, managing or preventing diseases that are ameliorated by inhibiting the interaction of β-cat and TCF4, such as cancer, neurodegenerative diseases, metabolic diseases, cardiovascular diseases, fibrosis and bone diseases. Background technique [0004] The canonical Wnt / β-cat signaling pathway is an important signal transduction pathway required for normal embryonic developme...

AI Technical Summary

Problems solved by technology

First, targeting the β-cat-TCF4 interaction is more effective in diseases with mutations in downstream components of the Wnt pathway, making upstream inhibitors less effective

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