Substituted 1-methyl-1,2,3,4-tetrahydroisoquinoline molecules as PCSK9 allosteric binders

摘要

The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X₁, X₂, Y, R¹, R², R^A, R^B and n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples.;