Caspase-4 inhibitors and uses thereof

Abstract

The present disclosure relates to compounds of Formula (I): ， and pharmaceutically acceptable salts thereof, wherein Ring A, G1, RC, X, RD1, RD2, and RD3 are as described herein, methods of preparation and intermediates useful in said preparation, methods of treatment and prevention (e.g., of Caspase-4 mediated diseases and disorders), and pharmaceutical compositions comprising same. Compounds of Formula (I), and pharmaceutically acceptable salts thereof, are designed as selective Caspase-4 allosteric inhibitors, sparing Caspase-1, and have also been found to be selective against Caspase-5 and are thus, in embodiments, considered dual Caspase-4 / 5- inhibitors. The present disclosure further relates to the Applicant's discovery of a new and allosteric human Caspase-4 binding pocket, and methods of binding to (and compounds inhibiting the activity of) same, methods of treatment and prevention, and pharmaceutical compositions comprising such compounds.