TREATMENT OF SCLERODERMA USING AN INHIBITOR OF CBP/CATENIN

摘要

The present disclosure relates generally to alpha-helix mimetic structures and specifically to alpha-helix mimetic structures that are inhibitors of β-catenin. The disclosure also relates to applications in the treatment of scleroderma, including diffuse systemic sclerosis and limited systemic sclerosis, and pharmaceutical compositions comprising such alpha helix mimetic β-catenin inhibitors.

主权项

1. An alpha helix mimetic β-catenin inhibitor compound for the treatment of scleroderma, having the following formula (I): wherein: A is —CHR7—,
wherein R7 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; G is —NH—, —NR6—, —O—, —CHR6— or —C(R6)2—,
wherein R6 is independently selected from optionally substituted alkyl, optionally substituted alkenyl and optionally substituted alkynyl; R1 is optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl or optionally substituted heterocycloalkylalkyl; R2 is -W21-W22-Rb-R20,
wherein W21 is —(CO)— or —(SO2)—; W22 is bond, —O—, —NH— or optionally substituted lower alkylene; Rb is bond or optionally substituted lower alkylene; and R20 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; and R3 is optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl; or a pharmaceutically acceptable salt thereof.